Alkynylphosphonates reactions

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

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). ... 

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... 

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. ... 

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. ... 

The effectiveness of dialkyl 1-aIkynylphosphonates as acelonyl equivalents for the preparation of dialkyl 2-oxoalkylphosphonates has long been established. Because 2-oxoaIkylphosphonates themselves are versatile synthetic intermediates, especially as the reagents of choice for promoting a number of Homer-Wadsworth-Emmons cyclization reactions, procedures that effect the direct conversion of dialkyl 1-alkynylphosphonates into dialkyl 2-oxoalkylphosphonates are of special importance. The procedure for the hydration of dialkyl 1-alkynylphosphonates has remained unchanged since the first report in 1966 (Scheme 1.21). Thus, treatment of diethyl 1-alkynylphosphonates with aqueous H2SO4 in MeOH in the presence of HgSO4 gives, after reflux for 15 h - ... 

The cycloaddition of 1-pyrrolidylcyclopentene with activated alkynes, such as dimethyl acctylcne-dicarboxylate, is reported to occur at room temperature. In contrast, the less reactive diethyl 1-alkynylphosphonates require reaction temperatures of at least 85°C to permit cycloaddition. Under such conditions, spontaneous ring opening of the thermally unstable cyclobutene intermediate yields the ring-enlarged product. Acid hydrolysis of the product enamine gives the unsaturated P-keto-phosphonate (Scheme 1.22). The best results for the cycloaddition are obtained with rigorous exclusion of moisture and with temperatures held below 100°C. Reaction times varied from 24 h (Rl = H) to 8 days (Ri = MOM). -... 

The reaction must be carefully controlled in order to optimize the yield. Cycloadditions with substituted diethyl 1-alkynylphosphonates are less satisfactory. ... 

In the second reaction type, the ene and yne functionalities are found in two different phosphorus substituents. These 1-alkynylphosphonates undergo facile Pd(OAc)2-LiCl-catalyzed cyclization to give oxaphospholanes in good yields (77-89%, Scheme 1.27) but with low stereoselectivity, ratios at the exo double bonds being approximately 60/40. ... 

Recently, the hydroboration of I -alkynylphosphonates with pinacolborane has been reported. However, the vinylphosphonoboronatcs so obtained are difficult to isolate, and they are immediately subjected to Suzuki coupling reactions with aryl iodides. Similarly, hydrophenylation of diethyl... 

Because of the ready accessibility of dialkyl 1-alkynylphosphonates, their isomerization to conjugated dienes represents a useful synthetic transformation. In the presence of Pd2(dba)3CHCl3, the thermal isomerization of diethyl 1-alkynylphosphonates into diethyl (lE.SEj-alkadienylphospho-nates occurs at 30°C in toluene, whereas at 110°C isomeric (2 ,3 )-alkadienylphosphonates are formed. The transfonuation is effected with good yields (79-92%) but requires lengthy reaction times (24-69 h). The same isomerization reaction can be effected with Bu3P. ... 

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. 

Sodium enolates of diethyl 2-oxoalkylphosphonates react with diethyl chlorophosphate to produce enol phosphates. Low-temperature treatment of enol phosphates with tert-BuOK induces the ()-elimination of potassium diethyl phosphate and formation of diethyl 1-alkynylphosphonates in good yields (43-95%, Scheme 7.113). However, the reaction is prone to prototropic isomerization and diethyl 2-oxobutyIphosphonate leads to a mixture of diethyl 1-butynyIphosphonate (43%) and diethyl 2-butynylphosphonate (51%). ... 

Bicvclic and Tricyclic Phosphoranes. - The reaction of phosphorocyanatidites (96ab) with alkylidene acetamide (97) proceed via the common intermediate (98) to form either (99, R= Me) by reaction with a second mole of (97) or (100) by dimerisation.30,31 An analogous dimerisation product (102) is also obtained with diphenyl carbodiimide (101)3 and the reactions of alkynylphosphonates with (101) are reported in the same paper. 

Trialkyl phosphites undergo reaction with alkynyliodonium tosylates, resulting in dialkyl alkynylphosphonates, 102, via an Arbuzov-type process [78] [Eq. (55)]. 

Mention should also be made of the addition of tervalent phosphorus compounds to alkynylphosphonic and to (alka-l,2-dienyl)phosphonic derivatives [in which addition occurs across the C(i)—C(2) bond]. The main product is of type 521 (X = Ph, OR or NR2), but is normally accompanied by smaller amounts of the isomers 522. Although this process is formally of a [3 + 2] format, a P NMR study of the kinetics suggests that the addition is not a synchronous addition but rather occurs in a stepwise manner . On the other hand, the phosphorylated Schiff base 523 undergoes regioselective and stereospecific reaction with a,j -unsaturated esters which, a kinetic study has shown, appears to be concerted. ... 

Reaction of dimethyl phosphonate (74) with the steroidal dienyl triflate 73 gave the dimethyl alkenylphosphonate 75 [23]. Dimethyl alkynylphosphonate (77) was produced in one step by the reaction of 1,1-dibromo-l-alkenes 76 with dimethyl phosphonate (74) in DMF using Pd(OAc)2-DPPF as a catalyst and propylene oxide as a scavenger of HBr. The expected monocoupling product, bromovinylphos-phonate, was not obtained [24]. Phosphonates 78 can be converted to arylphos-phines 79 by reaction with aryl Grignard reagents, followed by reduction with HSiCls [25]. 

Development of the acenaphthenequinone reactions 12H(85)1869. Diels—Alder reactions of fluorinated alkynylphosphonates to give fluori-nated heterocyclic organophosphonates 13JFC(152)29. N,N-Dimethylformamide A multipurpose building block 12AG(E) 9226. 

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]. 

Kazmaier and Jena have presented syntheses of stannylated, allyl (86) and vinylphosphonates (87) by molybdenum-catalyzed hydrostannation of the corresponding propargyl- (84) and alkynylphosphonate (85) derivatives (Scheme 27). " The stannylated phosphonates, obtained with high regios-electivities, were applied as building blocks in further modifications, such as Pd-catalyzed cross coupling reactions or iodination. 

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

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