Cyanomethylphosphonate

The synthetic 31 was converted to the cyanoglucoside osmaronin (41a) which was isolated from a methanolic extract of the leaves of Osmaronia cerasi-formis. Acetylation of 31 gave an acetate (99% yield) which was subjected to ozonolysis to afford a ketone 42. The Horner-Emmons reaction of 42 using diethyl cyanomethylphosphonate furnished (Z)-43a (22% yield from the acetate of 31) and ( )-43b (10% yield from the acetate of 31). Deprotection of (Z)-43a and ( )-43b gave the (3-D-glucosides 41a (83% yield) and 41b (94% yield), respectively. The spectral data of the synthetic 41a were identical with those ( H- and C-NMR) of the natural osmaronin (41a) (Fig. 5). 

Then the synthetic 32 was converted to the cyanoglucoside sutherlandin (44) which was isolated from leaves of Acacia sutherlandii. Acetylation of a diastereomeric mixture of 32 gave the corresponding acetate which was subjected to the hydrogenation and the subsequent oxidation to yield the a-acetoxyl ketone (45, 84% overall yield from the acetate of 32). The Homer-Emmons reaction of 45 using diethyl cyanomethylphosphonate furnished (Z)-46a (33% yield from 45) and ( )-46b (31% yield from 45). Deprotection of the presumably desired (Z)-46a afforded (Z)-44 (76% yield), whose C-NMR spectra were identical with those of the natural sutherlandin (44) (Fig. 6). 

Subsequent reduction of the alkylated cyanomethylphosphonates produces p-aminoethylphosphonates. Diethyl aminomethylphosphonates are C-alkylated with a range of agents via the initial formation of the imines [73],... 

The structure of the leukotrienes receptor antagonist cinalukast (58-9) bears only the vaguest resemblance to its predecessor, or, for that matter, to a leukotriene. Reaction of the cyanomethylphosphonate (58-1) with hydrogen sulfide converts the nitrile to a thioamide (58-2). Treatment of that intermediate with the bromoketone... 

The reaction of diethyl cyanomethylphosphonate in the presence of A1203 with aliphatic or aromatic aldehydes in the absence of solvent results mainly in the product of Knoevenagel reaction (equation II). 

It was reported that l,3-dithietane-2,4-diylidenebis(cyanomethylphosphonates) and -phenylphosphinates 92 underwent reaction with a variety of substituted acetonitriles 93 to afford phosphono- or phosphino-substituted 7-thiapyrones 94, in a one-stage process (Equation 13) <1998H(47)221>. 

Hachemi, M., Puciova-Sebova, M., Toma, S. and Villemin, D. Dry reaction of diethyl cyanomethylphosphonate and tetraethyl methylenediphosphonate with benzaldehyde on solid bases, Phosphorus, Sulfur Silicon Relat. Elem, 1996, 113, 131-136. 

L-proline followed by reaction of the product with diethyl cyanomethylphosphonate (1, 250 2, 130-131) gives 2 and 3 in a 1 1 ratio (18.3% total yield). Use of piperidine acetate gives 2 and 3 in a 1 22 ratio (50.3% total yield). Dibenzylam-monium trifluoroacetate shows similar selectivity 2/3 = 1 19 (76.4% total yield). However, use of morpholine-camphoric acid in ether-HMPT favors formation of 2. With this catalyst 2 and 3,are obtained in 37.5% and 1.5% yield, respectively. ... 

An important step in a synthesis of 3/i-acetoxy-5/i,14c -bufa-20,22-dicnolide from dchydroepiandrostene includes ihe condensation of the carbanion derived from diethyl cyanomethylphosphonate with the ketone (1), ... 

The reaction conditions necessary in order to obtain, in high yields and pure form, either 1-cyanomethylphosphonates or 1-cyanomethylenediphosphonates, has been reported. Catalytic systems derived from Ru(CO) porphyrins are extremely efficient at converting styrene and diisopropyl diazomethylphosphon-ate to cyclopropyl phosphonate esters (172) in high yields and with high stereoselectivity. A monocarbene complex Ru(TPP)(CH P(0)(0iPr) 2) has been isolated as a possible catalytically active species. ... 

Diethyl cyanomethylphosphonate, (CjH50)2P CH2CN. Mol. wt. 177.17. Supplier Aldrich. 

Cyclopropanes Diborane. Diethylaluminum iodide. Diethyl cyanomethylphosphonate. Dlphenyldiazomethane. Lithium ahitninum hydride. Simmona-Smith reaction. Sodium hydride. Triethylphoiphoenol pyruvate. 

While the diethyl benzylphosphonate anion did not react with phenyloxirane, even though the anion was prepared in situ, the diethyl cyanomethylphosphonate anion gave 2-phenylcy-clopropane carbonitrile in 51% yield. ... 

Homer-Wadswortli-I ininions Reactions of Dialkyl Cyanomethylphosphonates Preparation of a,P-l[nsaturated Nitriles... 

A -FluorohiXtrifluoromethanesulfonyl)imide is one of the most powerful electrophilic fluori-nating agents. It was successfully used to fluorinate diethyl cyanomethylphosphonate in the presence of w-BuLi (1 eq), and the resulting diethyl 1-fluoro-1-cyanomethylphosphonate can be isolated (51% yield) or metallated in situ and reacted with carbonyl compounds in a Homer-Wadsworth-Emmons reaction to give a-fluoroacrylonitriles in 30-58% overall yields (Scheme 3.21). 2 These results aie especially noteworthy because the fluorination of diethyl cyanomethylphosphonate with NFBS in the presence of LiHMDS (2 eq) produces the A -fluoro and not the expected C-fluoro phosphonate. 

The cyanomethylphosphonates are readily available reagents, on laboratory scale or commercially. Since their first preparation, they have given rise to a surprisingly large number of synthetic applications. This chapter describes their preparations and their reactions including preservation and removal of the phosphoryl group. 

Dawson and Burger first demonstrated that the Michaelis-Arbuzov reaction of chloroacetonitrile and triethyl phosphite furnishes diethyl cyanomethylphosphonate. In its most general form, it involves the addition of triethyl phosphite to chloroacetonitrile at 150-170°C to give diethyl cyanomethylphosphonate in up to 80% yields (Scheme 6.2). ° This procedure has been developed on an industrial scale The use of bromo- or iodoacetonitrile (X = Br, I, Scheme 6.2) was also reported. The reaction may be used to prepare any dialkyl cyanomethylphosphonate, and a variety of trialkyl phosphites have produced the corresponding phosphonates in reasonable to good yields (29-90%, Scheme 6.2). " Cyclic phosphites, 4,5-dimethyl-2-methoxy-l,3,2-dioxaphos-pholane (meso and racemic) and 5,5-dimethyl-2-methoxy-l,3,2-dioxaphosphorinane, react with chloroacetonitrile to produce 5- and 6-membered cyclic phosphonates in 50% and 72% yields, respectively. ... 

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