- METHODS FOR NUCLEOPHILIC FLUOROMETHYLATION
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A novel, convenient and efficient method for trifluoromethylation of substrate compounds is disclosed. Particularly, alkoxide and hydroxide induced nucleophilic trifluoromethylation of carbonyl compounds, disulfides and other electrophiles, using phenyl trifluoromethyl sulfone PhSO2CF3 (or sulfoxide PhSOCF3) is disclosed. A method of both symmetrical and unsymmetrical anti-2,2-difluoropropan-1,3-diols with high diastereoselectivity (up to 94 % de) is disclosed using dufluoromethyl phenyl sulfone. This unusual type of high diastereoselectivity was obtained via an intramolecular charge-charge repulsion effect rather than the traditional steric control (based on the Cram's rule). Thus, difluoromethyl phenyl sulfone can be used as a novel difluoromethylene dianion species (`CF2""), which can couple two electrophiles (such as diphenyl disulfide or non-enolizable aldehydes) to give new difluoromethylenated products.
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- Alkoxide- and hydroxide-induced nucleophilic trifluoromethylation using trifluoromethyl sulfone or sulfoxide
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(Matrix presented) The first alkoxide- and hydroxide-induced nucleophilic trifluoromethylation of carbonyl compounds, disulfides, and other electrophiles, using phenyl trifluoromethyl sulfone 1a (sulfoxide 1b) is reported. The trifluoromethyl sulfone 1a or sulfoxide 1b acts as a CF3 - synthon. Both sulfone 1a and sulfoxide 1b are commercially available and can also be conveniently prepared from trifluoromethane. The new methodology provides a convenient route for efficient trifluoromethylation.
- Prakash, G. K. Surya,Hu, Jinbo,Olah, George A.
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p. 3253 - 3256
(2007/10/03)
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- Electroorganic Chemistry. 130. A Novel Trifluoromethylation of Aldehydes and Ketones Promoted by an Electrogenerated Base
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A base generated by the electroreduction of 2-pyrrolidone deprotonated trifluoromethane to form a trifluoromethyl anion equivalent.In the presence of hexamethyldisilazane, this species reacted with a variety of aldehydes and ketones to afford (trifluoromethyl)-carbinols in high yield.
- Shono, Tatsuya,Ishifune, Manabu,Okada, Toshio,Kashimura, Shigenori
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- The reduction of aryl trifluoromethyl ketones by sodium borohydride. The hydride transfer process
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The rates of reduction of 17 aryl trifluoromethyl ketones by sodium borohydride in 2-propanol have been measured.The rho (ρ) value is 3.12, excluding the 4-amino and 4-dimethylamino groups, which both lower the rate to a greater extent than their ? values predict.The close correspondence between substituent effects for hydride addition in the methyl and trifluoromethyl series (excluding the amino groups) suggests that normal substituent effects are to be expected for oxidation processes involving hydride removal in trifluoromethyl compounds.The present results are consistent with the oxidation of aryl trifluoromethyl carbi ols by permanganate taking place by hydrogen atom abstraction.The effect of substituents on the rate of reduction of the trifluoromethyl ketones is almost identical to that on the equilibrium constant for formation of the ketone hydrates.The application of the reactivity-selectivity principle to the reduction reaction is also considered.Reduction of the 4-ethyl compound has ΔH = 2.7 kcal mol-1 and ΔS = -38 cal deg-1 mol-1.
- Stewart, Ross,Teo, K. C.
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p. 2491 - 2496
(2007/10/02)
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- The reduction of aryl trifluoromethyl ketones by N-carbamoylmethyl-1,4-dihydronicotinamide
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The reaction of 15 aryl trifluoromethyl ketones with N-carbamoylmethyl-1,4-dihydronicotinamide has been studied in aqueous sulfolane buffer.The unsubstituted ketone and those containing electron-withdrawing groups in the ring have the following reaction characteristics: (a) a high yield of alcohol is obtained, (b) the observed reaction rate is independent of ring substituent; however, when corrections are made for degree of hydration of the ketones the rate is correlated with Hammett ? values with a rho of 1.98, (c) a secondary isotope effect of approximately 1.08 and primary isotope effects of 1.45-1.62 are observed at 43.4 deg C for the reaction of the dihydronicotinamide containing one or two atoms of deuterium at C-4, (d) ΔH = 15.2 kcal mol-1, and ΔS = -27.0 cal deg-1 mol-1 for the unsubstituted compound, uncorrected for ketone hydration; ΔS for reaction of the unhydrated ketone and dihydronicotinamide is estimated to be -45 to -50 cal deg-1 mol-1.The mechanism for the reduction is consistent with hydride transfer from reductant to oxidant, very possibly accompanied by blind-alley formation of an adduct between ketone hydrate and dihydronicotinamide.Ketones containing electron-donating groups in the ring react with the dihydronicotinamide in some undetermined way, giving little or no alcohol as product.
- Stewart, Ross,Teo, K. C.,Ng, L. K.
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p. 2497 - 2503
(2007/10/02)
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