Synthesis of esters of α-chloroacetoxy-β,β,β,-trichloroethylphosphonic acids

Summary The synthesis of 11 previously unreported dialkyl esters of -mono-, -di-, and -trichloroacetoxy-,,-trichloroethylphosphonic acids has been effected.     

Synthesis of new α,α,β,β-tetrafluoroesters

Substituted phenyl iodides or diiodides reacted with ethyl iodotetrafluoroproponylate ICF₂CF₂CO₂Et, 1 in the presence of copper powder to give the coupled products 2 or 3 in good yields. Addition of 1 to ethylene and allyl acetate proceeded smoothly under thermal and radical conditions to give the corresponding adducts, which underwent elimination reaction to give β-vinyl and β-allyl α,α,β,β-tetrafluoroesters, CH₂CHCF₂CF₂CO₂Et, 4 and CH₂CHCH₂CF₂CF₂CO₂Et, 5, respectively. 1 also readily reacted with 1,5-hexadiene and 1-hexene with copper or palladium complex, followed by reduction to remove iodine to produce ω-alkenyl-α,α,β,β-tetrafluoroester CH₂CH(CH₂)₄CF₂CF₂CO₂Et 6 and α,α,β,β-tetrafluoroester C₄H₉CH₂CHICF₂CF₂CO₂Et.     

Synthesis of 15β, 16β-methyleneprogesterone

15,16-Methyleneprogesterone was produced from 15,16-methylene-3-hydroxyandrost-5-en-17-one with Wittig olefination of 17-ketone by methoxymethylenetriphenylphosphorane as the key stage.Translated fromIzvestiya Akademii Nauk, Seriya Khimicheskaya, No. 1, pp. 203–207, January, 1993.     

Stereoisomerism ofβ-polyfluoroalkyl-α,β-enones

-Polyfluoroalkyl-,-enones formed in the E,Z form are converted by the action of atmospheric oxygen into a 937 mixture of E,Z and Z,E isomers in the dark and 6040 mixture of these isomers in the light. The Z isomer of 1-phenyl-4,4, 4-trifluoro-2-buten-1-one was isolated preparatively for the first time and its E conformation relative to the C-C bond was established. The Z,E isomer spontaneously transforms into the indicated equilibrium mixtures.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 7, pp. 1685–1689, July, 1991.     

Synthesis and reactivity of alkenyl- and alkynyl-substituted β,β-dihalo-and β,β,β-trichloroamines

β,β-Dihalo- and β,β,β-trichloroamines, obtained by Lewis acid-promoted Petasis-type reaction of α,α-dichlorinated and α,α,α-trichlorinated imines or reduction of α,α-dihaloaldimines, were subjected to a reactivity study and turned out to be remarkably stable compounds. In general, only the bases KO^tBu and NaOMe cause a 1,2-dehydrochlorination with formation of unsaturated α-chloroimines or unsaturated α,α-dichloroimines. Hydrolysis of the α-chloroimines with aqueous oxalic acid resulted in the formation of the corresponding unsaturated α-chloroketones. The reaction of simple β,β-dihaloamines with NaOMe and KO^tBu generated 2-haloprop-2-enylmines and 2,2-dimethoxypropylamines.     

Synthesis of β-Fluoroalkyl-β,β-dimethoxy Ketones and β-Fluoroalkyl-β-methoxy-α,β-enones

α-Bromo-β-fluoroalkyl-α,β-enones react with sodium methoxide in methanol to give the corresponding β-fluoroalkyl-β,β-dimethoxy ketones which eliminate methanol molecule to produce a mixture of E/Z-isomeric β-fluoroalkyl-β-methoxyvinyl ketones, the Z isomer prevailing.     

Synthesis of 6-chloronicotinates of steroidal 3β,5α,6β-triols and 3β,5-dihydroxy-6-ketones

New esters of 3β,5α,6β-trihydroxysteroids and 3β,5-dihydroxy-6-ketosteroids containing 6-chloropyridine groups characteristic of the alkaloid epibatidine were synthesized by acylation with 6-chloronicotinoylchloride. Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 175-179, March-April, 2009.     

Synthesis of bis-β,β′-spiro-pyrrolidinyl-oxindoles,containing a rhodanine fragment

The synthesis of isatilidene derivatives of N-alkylrhodanines has been carried out with dipolarophiles and unstable azomethine ylides, generated in situ from sarcosine and paraformaldehyde. A series of chiral pyrrolidinyl-oxindoles spirofused in the β,β′-positions has been synthesized in the result of cycloaddition in high yield and diastereoselectivity.     

Novel Synthesis of 2β,3β,20β-Triacetoxy-5 -pregnan-6-one

Pregnenolone (2) is used in a novel synthesis of 2,3,20-triacetoxy-6-ketosteroid (6), a key intermediate in the preparation of 20-hydroxyecdysone (1)     

Bromination of polyfluorinated α,β-enones

Polyfluoroalkyl-,-enones readily add Br₂ to give ,ß-dibromoketones. The latter are readily and regioselectively dehydrobrominated to -bromo-,-enones on treatment with K₂CO₃ or NEt₃ Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2134–2136, December, 1993.     

β,β-Difluoro analogs of α-oxo-β-phenylpropionic acid and phenylalanine

A simple three-step procedure converted the readily accessible (2-bromo-1,1-difluoroethyl)arenes (2) into α-aryl-α,α-difluoroacetaldehydes (1). Subsequent hydrocyanation, hydrolysis, oxidation and again hydrolysis afforded β-aryl-β,β-difluoro-α-oxopropionic acids (3). Reductive amination transformed the oxoacids 3 into a separable mixture of α-hydroxyacids 11 and racemic β,β-difluoro-β-phenylalanine derivatives (4). Enantiomerically pure β,β-difluorophenylalanine (l-4a) was obtained when α,α-difluoro-α-phenylacet-aldehyde (1a) was condensed with homochiral 1-phenylethylamine, hydrogen cyanide added to the resulting imine, the diastereomeric mixture thus produced hydrolyzed to the carboxamides (15) which were found to be separable by fractional crystallization or chromatography. The pK_a values of the β-aryl-β,β-difluoroalanines (4) were measured and biological profile of the latter probed. 3-(4-Chlorophenyl)-3,3-difluoro-2-oxopropionic acid (4c) proved to be a potent (K_i 27 μM) and selective inhibitor of arogenate dehydratase, a key enzyme catalyzing the last step of the phenylalanine biosynthesis.     

Synthesis of β,β‘-Difluorinated and β,β’-F-Dialkylated Acetals

Using the phase transfer catalysis technique, a series of fluorinated acetals has been prepared, in basic medium, by action of dicholromethane on 2-mononfluorinated alcohols or 1-F-alkyl 2-fluoroethanols. The identification of these new acetals has been achived by the study cf their ¹H, 19F NMR and their mass spectra.     

Catalytic diastereoselective reduction of α,β-epoxy and α,β-aziridinyl ynones

The Noyori transfer hydrogenation of α,β-epoxy and α,β-aziridinyl ynones leads to the corresponding α,β-epoxy or α,β-aziridinyl propargylic alcohols with high reagent-controlled diastereoselectivity.     

Synthesis of new α-chloropyridine derivatives of steroidal 3β,5α,6β-triols and 3β,5-dihydroxy-6-ketones

New steroid derivatives containing 6-chloropyridine groups characteristic of the alkaloid epibatidine and neonicotinoid insecticides were synthesized by reacting 3β,5α,6β-trihydroxysteroids or 3β,5-dihydroxy-6ketosteroids with 2-chloro-5-chloromethylpyridine. Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 180-182, March-April, 2009.     

Photochemical addition of diethyl ether to β,β,β',β'-tetrakis(trifluoromethyl)divinyl ether

The 1:1 adducts of diethyl and ,,','-tetrakis(trifluoromethyl)divinyl ether (1),i.e., 3,5-(ee)-bis[2,2,2-trifluoro-1-(trifluoromethyl)ethyl]-2,6-dimethyl-1,4-dioxane (2) (3 isomers) and 4-ethoxy-1,1,1-trifluoro-2-trifluoromethyl-3-[3,3,3-trifluoro-2(trifluoromethyl)propenyloxy]pentane (3), have been obtained by UV-irradiation of a solution of divinyl ether1 in diethyl ether. The X-ray structural investigation of the all-(e)-isomer of dioxane (2) has been carried out.Deceased.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 85–88, January, 1994.