Phosphonates 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. ... 

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 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). -... 

Bromo- and iodotrimethylsilane, reagents compatible with alkyne and other functionalities, are suitable for the mild P-0 dealkylation of dialkyl 1-alkynylphosphonates to give the corresponding phosphonic acids.The greater reactivity of iodotrimethylsilane will probably prove advantageous for the low-temperature dealkylation of phosphonates having triple bonds. However, transesterification of diethyl 2-propynylphosphonate with iodotrimethylsilane at -30°C followed by solvolysis with MeOH led quantitatively to the 1-propynylphosphonic icid. ... 

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. ... 

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

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]. 

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. 

An example of Cp RuQ(cod)-catalyzed homo Diels Alder [2+2+2] cycloaddition of alkynylphosphonates with norbomadiene providing the corresponding phosphonate substituted deltacyclenes was also described [133] [Eq. (63)]. This reactivity was found to be dependent on the presence of the phosphonate moiety. 

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. 

Synthesis of phosphonic acids and their derivatives An efficient and remarkably clean practical procedure for allqmylation of dialkyl phosphites with readily available, bench-stable copper acetylides (314) has been reported by Evano et In the presence of iV-methyli-midazole (NMI) as a ligand, corresponding alkynylphosphonates (315) have been readily obtained in good to excellent yields at room temperature and in a multigram scale (Scheme 85). 

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. 

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