Mayumi Koyama

Reactions of trifluoromethyl ketones. IX. Investigation of the steric effect of a trifluoromethyl group based on the stereochemistry on the dehydration of trifluoromethyl homoallyl alcohols

Abstract In a previous paper we reported that a trifluoromethyl group behaves as a larger substituent than a butyl or a phenyl group and slightly larger than a sec-butyl group in ene reactions of trifluoromethyl carbonyl compounds. Dehydration of trifluoromethyl homoallyl alcohols, which are obtained by the ene reaction of trifluoromethyl ketones, has now been extensively investigated to compare further the steric effect of a trifluoromethyl group with those of other substituents. A trifluoromethyl group behaves as a substituent as large as a cyclohexyl group and a little smaller than a sec-butyl group. Differences between steric effects in the ene reaction and in the dehydration are discussed.

Ene-type reaction of trifluoroacetaldehyde hemiacetal with ene compounds in the presence of a Lewis acid

Abstract Reaction of trifluoroacetaldehyde ethyl hemiacetal with ene compounds in the presence of a Lewis acid gives α-trifluoromethylated homoallyl alcohols, the same products as those from the ene reaction of trifluoroacetaldehyde, in moderate to good yields. Boron trifluoride etherate was found to be most effective in this reaction. This method eliminated many difficulties encountered on the ene reaction of trifluoroacetaldehyde, which is a gas at room temperature and polymerizes to insoluble polymer in the presence of a Lewis acid.

SYNTHESIS OF A FLUORINE ANALOG OF HEMATOPORPHYRIN BY RING CLOSURE

Abstract Benzyl 3,5-dimethyl-2-pyrrolecarboxylate (1) was converted to 4-(2,2,2-trifluoro-1-hydroxyethyl) derivative (2) on treatment with trifluoroacetaldehyde ethyl hemiacetal in the presence of zinc chloride. After protection of the hydroxyl group with a methyl group, 2 was converted to benzyl 4-methyl-3-(2,2,2-trifluoro-1-methoxyethyl)-2-pyrrolecarboxylate (9) and benzyl 5-acetoxymethyl-3-methyl-4-(2,2,2-trifluoro-1-methoxyethyl)-2-pyrrolecarboxylate (10). Both esters were condensed to dipyrrylmethane compound 11, which was debenzylated, decarboxylated, and condensed with a bottom half of the porphyrin to give hexafluorohematoporphyrin derivative 14, potentially useful for photodynamic therapy of cancer.

Trifluoromethylation of Tocopherols

Abstract γ- and δ-Tocopherol were converted to iodo compounds, which were trifluoromethylated with trifluoromethyl iodide and copper powder in HMPA.

Diels-Alder reactions of trifluoromethyl dienes obtained from ene reactions of trifluoromethyl carbonyl compounds☆

Abstract The ene reactions of trifluoromethyl carbonyl compounds give products which may be dehydrated to trifluoromethyl dienes; the Diels Alder reaction of these have been investigated. The dienes from trifluoromethyl ketones hardly reacted, probably because the steric effect of the trifluoromethyl group prevents the diene from taking up a cisoid form. Dienes obtained from the ene reaction of trifluoroacetaldehyde have one substituent at a terminal position and react with dienophiles to give trifluoromethylated cyclohexene derivatives.

Synthesis of fluorine analogs of hematoporphyrin

With the aim of obtaining a porphyrin derivative useful for diagnosis and therapy of cancer, fluorine analogs of hematoporphyrin, which had trifluorohydroxyethyl group(s) in the place of hydroxyethyl groups, were synthesized by the reaction of deuteroporphyrin dimethyl ester with trifluoroacetaldehyde in the presence of aluminum chloride. Preliminary results of biological tests of the products showed that the hexafluoro analog of hematoporphyrin accumulates to Human liver cancer cells more selectively than other fluorine analogs

Synthesis of Trifluoromethylated Tetrahydropyrans from Ene Reaction Products of Trifluoromethyl Ketones: Synthesis of Fluorine Analogs of a Sesquiterpene

As the extension of the ene reaction of trifluoromethyl ketones, α-trifluoromethylated tetrahydropyrans, including fluorine analogs of sesquiterpenes, were synthesized from trifluoromethylated homoallyl alcohols, the products of the ene reaction

Synthesis of fluorine compounds using zinc complex of halothane

Abstract We have reported the Grignard reaction of Halothane, 2-bromo-2-chloro-1,1,1-trifluoroethane (1), with ketones gave unexpected products, α-(1-bromo-1-chloro-2,2,2-trifluoroethyl)alcohols (4) at a low temperature. However, this reaction hardly proceeded with aldehydes. Now, we found the reaction of 1 with aldehydes in the presence of zinc gave not only products of type 4, but α-(1-chloro-2,2,2-trifluoroethyl)alcohols (3), the expected type of products, under mild conditions in good to moderate yields.

A new method for synthesis of fluorine compounds using an unusual Grignard reaction of halothane with ketones

Abstract The reaction of 2-bromo-2-chloro-1,1,1-trifluoroethane (1) with 2-octanone (3a) in the presence of magnesium did not give 2-chloro-1,1,1-trifluoro-3- methyl-3-nonanol (4a) but 2-bromo-2-chloro-1,1,1-trifluoro-3-methyl-3- nonanol (5a) and 2-chloro-1,1-difluoro-3-methyl-1-nonen-3-ol (6a). This suggested that the primary Grignart reagent, 1-chloro-2,2,2-trifluoroethylmagnesium bromide (2), reacted with excess 1 rather than with the ketone 3a to give 1-bromo-1-chloro-2,2,2-trifluoroethylmagnesium bromide (8), which added to the ketone to give 5a. Detection of 1,1,1-trifluoro-2-chloroethane supported this mechanism. Compound 5a was formed preferentially at −53 °C, and on warming to 0 °C, the amount of 5a decreased while that of 6a increased. Therefore, compound 6A must be formed by reduction of 5a with excess magnesium. Treatment of 6a with hydrogen fluoride gave 2-chloro-1,1,1-trifluoro-3-methyl- 2-nonene (9a). Cyclohexanone (3b) and acetophenone (3c) reacted similarly to give corresponding products.

Synthesis of trifluoromethylated tetrahydropyrans from ene reaction products of trifluoromethyl ketones: synthesis of fluorine analogues of sesquiterpenes

Abstract Ene reaction of trifluoromethyl ketones were investigated extensively, 1) and the ene reaction products were transformed to many types of trifluoromethyl compounds. 2) Among these research, the ene reaction products of trifluoromethyl ketones were converted to α-trifluoromethylated tetrahydrofurans. In this study, derivatization of the ene reaction products to α-trifluoromethylated tetrahydropyrans were accomplished. Therefore, treatment of esters of 3,4-unsaturated alcohols with trifluoromethyl ketones gave α-(trifluoromethyl)homoallyl alcohol derivatives, which were hydrolyzed to 2,3-unsaturated 1,5-diol compounds. These were oxidized to δ-ketoalcohols. Hydrogenation of these alcohols, followed by treatment with Grignard reagents, gave trifluoromethylated 1,5-diols, which were dehydrated and cyclized to α- trifluoromethylated tetrahydropyran derivatives, some of which are fluorine analogues of curcumene ether, a sesquiterpene.