Milos Hudlicky

New stereospecific syntheses and x-ray diffraction structures of (−)-D-- and (+)-L--4-fluoroglutamic acid

Abstract Stereospecific syntheses of (+)-L- threo and (−)-D- erythro -4-fluoroglutamic acid are based on the hydrolysis of methyl 1-acetyl-4-fluoro-L-pyrrolidin-5-one-2-carboxylate, prepared from trans - and cis -4-hydroxyprolines, respectively.

Hydrogenolysis of carbon-fluorine bonds in catalytic hydrogenation

Abstract In contrast to the strong stability of saturated fluorine compounds in catalytic hydrogenation, allylic and vinylic fluorine atoms are displace by hydrogen relatively readily. Hydrogenolysis of carbon-fluorine bonds accompanies addition of hydrogen across double bonds in methyl 4-fluoro-3-methyl-2-pentenoate, in fluoromaleic, fluorofumaric, difluoromaleic and difluorofumaric acids. The extent of hydrogenolysis is affected by the catalyst and by the solvent. A concerted mechanism is offered to explain the readiness of the hydrogenolysis in allylic and vinylic fluorides.

Reaction of epoxides with diethylaminosulfur triflouride

Abstract Diethylaminosulfur triflouride (DAST) reacts with epoxides (oxiranes) to form geminal diflourides, vicinal diflourides, and bis(2-fluoroalkyl) ethers. Thus cyclopentene oxide gave cis -1,2-difluorocyclopentane and bis(2-fluorocyclopentyl) ether; cyclohexene oxide gave cis -1,1-difluorocyclohexane and bis(2-fluorocylohexyl) ether; styrene oxide gave 1,1-difluoroethylbenzene and 1,2-difluoroethylbenzene; and cis - and trans -stilbene oxides gave mixtures of meso - and racemic 1,2-difluoro-1,2-diphenylethanes together with 1,1-difluoro-2,2-diphenylethane resulting from a rearrangement. Cyclooctene oxide and cyclohexene sulfide do not react appreciably under the same conditions.

Catalytic hydrogenolysis of carbon-fluoride bonds: π bond participation mechanism

Abstract A new mechanism with the participation of π bonds is proposed to account for a relatively easy hydrogenolysis of carbon-fluoride bonds in catalytic hydrogenation of allylic, vinylic, benzylic and aromatic fluorides. This cyclic mechanism can also underlie some unusual results of hydrogenation of other halogen compounds.

Chemical shifts of fluorine in hydrogen fluoride and fluoride ion

Abstract Chemical shifts of fluorine in solutions of hydrogen fluoride, sodium fluoride, potassium fluoride, cesium fluoride, silver fluoride, silver bifluoride, ammonium bifluoride, and tetraethylammonium fluoride have been measured. Hydrogen fluoride was dissolved in water and in aqueous and anhydrous organic solvents (methanol, ethylene glycol, dimethoxyethane, carbitol (diethyleneglycol monoethyl ether), tetrahydrofuran, dioxane, dimethylformamide, acetonitrile, dimethylsulfoxide, and sulfolane (tetramethylene sulfone); all other fluorides were dissolved in water and aqueous organic solvents. The effects of fluoride concentration in water and in aqueous organic solvents on chemical shifts of fluorine were investigated.

Synthesis of fluorinated α-diketones and some intermediates

Abstract Reactions of perfluoroalkylcopper compounds with α-ketoacyl chlorides were used for the synthesis of fluorinated α-diketones. Heptafluoropropylcopper prepared from copper bronze and 1-iodoheptafluoropropane reacted with benzoylformyl chloride to give heptafluoro-1-phenyl-1,2-pentanedione, with trimethylpyruvyl chloride to give 2,2-dimethyl-5,5,6,6,7,7,7-heptafluoro-3,4-heptanedione, and with 3,3,4,4,5,5,5-heptafluoro-2-ketopentanoyl chloride or oxalyl chloride to give tetradecafluoro-4,5-octanedione. Syntheses of fluorinated acetylenes, cyanohydrins, α-hydroxy acids, α-keto acids, their chlorides, and other intermediates for the syntheses of α-diketones by the above route and by other methods are described. An interesting seven-membered ring containing β-hydroxy ketone was obtained by an intramolecular aldol condensation of a fluorinated bis(methyl) ketone.

Reduction of Vinyl Halides to Alkenes, and of Aryl Halides and Related Compounds to Arenes

Unlike most reductions of organic compounds, hydrogenolysis of the bond between trigonal carbon and a halogen does not possess many synthetic applications. Who would be interested in converting, for example, laboriously prepared iodobenzene to benzene by replacing iodine by hydrogen? However, the knowledge of reaction conditions for hydrogenolysis of halogen compounds is frequently useful for preventing such a reaction during reductions of other functions in an organic molecule.

Synthesis of fluorinated α-diketones and as-triazines and quinoxalines

Abstract Benzylheptafluoropropyl ketone and 1,8-diphenyl-3,3,4,4,5,5,6,6-octafluoro-2,7-octafluoro-2,7-octanedione were prepared by the reaction of benzylmagnesium chloride with heptafluorobutyric acid and octafluoroadipic acid, respectively. Oxidation of the methylene ketones with selenium dioxide produced 1-phenyl-3,3,4,4,5,5,5-heptafluoro-1,2-pentanedione and 1,8-diphenyl-3,3,4,4,5,5,6,6-octafluoro-1,2,7,8-octanetetrone. Both α-diketones were yellow and readily formed crystalline hydrates. Several alternate routes to the synthesis of the fluorinated α-diketones were investigated. The α-diketones were reacted with amidrazones and aromatic o -diamines to form as -triazines and quinoxalines, respectively.

Practical preparation of some potentially anesthetic fluoroalkanes : regiocontrolled introduction of hydrogen atoms

Abstract Methods are described for the large-scale preparation of a number of fluoroalkanes, which have been tested for general anesthesia.

Dehydrohalogenations of cis- and trans-1-bromo-2-flourocyclohexanes

Abstract Reactions of both diastereomeric vicinal bromofluorocyclohexanes with sodamide, sodium methoxide, potassium tert -butoxide, and triethylamine were studied. cis -1-Bromo-2-fluorocyclohexane eliminated almost exclusively hydrogen bromide giving mainly 1-fluorocyclohexene and a small amount of 3- fluorocyclohexene. trans -1-Bromo-2-fluorocyclohexane eliminated preferentially hydrogen fluoride on treatment with sodamide. Potassium tert - butoxide eliminated hydrogen bromide and yielded 3-fluorocyclohexene and a small amount of 1,3-cyclohexadiene, whereas sodium methoxide converted trans -1-bromo-2-fluorocyclohexane to 3-fluorocyclohexene and 3-methoxycyclohexene. Possible mechanisms and stereochemistry of the preferential elimination of hydrogen fluoride are discussed and new interpretations are offered.