G. Alvernhe

Synthesis of β-chloro(trifluoromethyl)acroleins and a specific reaction towards β-aminothiols

Abstract β-chloro-β-(trifluoromethyl)acroleins and β-chloro-α-(trifluoromethyl)-acrolein have been synthesized through Vilsmeiers reaction. A specific 1,4-addition of the nitrogen atom from β-aminothiols is observed.

New processes for the halofluorination of norbornadiene. Structural reexamination of the products. Evidence for exclusive exo attack by electrophiles

Abstract The bromofluorination of norbornadiene using NBS in the presence of the new fluorinating agent Et3N/3HF leads to a 3:2 mixture of 3-exo-bromo-5-exo-fluoronortricyclane 1 and 3-exo-bromo-5-endo-fluoronortricyclane 2 . The structures of these compounds were proven by independent syntheses and extensive NMR spectroscopic studies. The structure (3-endo-bromo-5-exo-fluoronortricyclane) given for the minor compound in the literature10 was revised especially in terms of the comparison of 3JCF coupling constants in the 13 C NMR spectra of both compounds. No evidence for an endo attack of the bromonium species on norbornadiene as stated in the literature10 was observed.

Synthesis of monofluorinated C4-building blocks based on methallyl chloride

Halofluorination of methallyl chloride using N-halosuccinimides in combination with triethylamine trishydrofluoride (Et3N·3HF) gave in each case more than 98% of the Markovnikov products and <2% of the regioisomers in good yield. The formal addition of methanesulfenyl fluoride with the combination of dimethyl(methylthio)sulfonium fluoroborate (DMTSF) and Et3N·3HF gave a 94:6 mixture of both regioisomers. Only small phenylsulfenyl fluorination of methallyl chloride has been observed when treated with N-phenylthiophthalimide (NPTP) and Olahs reagent. With benzenesulfenyl chloride, 1,3-dichloro-2-methyl-2-(phenylthio)propane is formed which on treatment with Olahs reagent at 0 °C or with Et3N·3HF at 60 °C rearranges to 1,2-dichloro-2-methyl-2-(phenylthio)propane. Treatment of 1,3-dichloro-2-methyl-2-(phenylthio)propane with silver fluoride in methylene chloride at −30 °C gave 1-chloro-2-fluoro-2-methyl-3-(phenylthio)propane which was also obtained by reaction of 1-bromo-3-chloro-2-fluoro-2-methylpropane with thiophenolate. n nChlorofluorination of methallylphenylthio ether using NCS/Et3N·3HF failed, while corresponding reactions with NBS or NIS and Et3N·3HF gave mainly the bromo- or iodo-fluorides with Markovnikov orientation in 61% or 35% yields. Related halofluorinations of methallylphenyl ether gave the halofluorides in good yield. All attempts to obtain chromanes or thiochromanes bearing a 3-fluorine substituent by cyclization of these halofluorinated ethers or thio ethers failed using different Lewis acids. However, the benzyl protected o-allylphenol which was bromofluorinated with NBS/Et3N·3HF in good yield gave on catalytic hydrogenation over Pd/C the 3-fluoro-2H-chromane in nearly quantitative yield.

Synthese de fluoro-3 azacyclanes : action de l'acide fluorhydriqiue sur les aza-1 bicyclo [n.1.0] alcanes

Abstract The addition of liquid hydrogen fluoride or Olahs reagent (pyridin-10 HF) to 1-aza bicyclo [n.1.0] alkanes leads to the formation of 3-fluoro 1-aza heterocyclic compounds. Isomeric 3-fluoro azetidines, 3-fluoro piperidines and a 3-fluoro azepine have been prepared by this procedure.

Reactivity of β-(trifluoromethyl) acroleins towards primary alkyl (or aryl) amines: synthesis of (trifluoromethyl)-1-aza-1,3-dienes and secondary (trifluoromethyl) allylamines

Abstract Vilsmeiers reaction on trifluoroketones leads to β-chloro-β-(trifluoromethyl)acroleins. The addition of primary alkyl- or aryl-amines to these acroleins leads in all cases to the formation of stable (trifluoromethyl)-1-aza-1,3-dienes which can be transformed quantitatively into secondary (trifluoromethyl) allylamines by reduction with sodium borohydride.

Synthesis of β-fluoroalkyl phenyl (or methyl) thioethers by sulfur-assisted halogen exchange with triethylamine tris-hydrofluoride

Abstract The exchange of chlorine in β-chloroalkyl phenyl (or methyl) thioethers by fluorine, with anchimeric assistance of sulfur, is very easily realized with the almost neutral fluorinating reagent, Et 3 N.3HF. The ‘one-pot’ reactions of alkenes with sulfenyl chlorides and subsequently with Et 3 N.3HF lead to the corresponding β-fluoroalkyl thioethers in high yields.

Addition d'amino-esters ou d'α-hydroxy-esters sur des azirines.

Abstract Addition of α-amino-esters or α-hydroxy-esters to azirines is studied. Two molecules of 2-methyl-3-phenyl 2H-azirine react with one molecule of α-hydroxy-ester ; a 1,3 dipolar addition is presumed.

Trifluoromethyl substitution affects the regiochemistry of cyclising condensation in 1,4 substitution processes

Abstract β-Trifluoromethyl β-chloroacrolein 2 reacts with 2-mercaptoethylamine 3 to produce thiazolidine 5 instead of the expected thiazepine 8 . The reason of this behaviour is the formation of the tetrahedral intermediate 6 because of stabilisation by the trifluoromethyl group ; an intramolecular substitution takes place faster than a 1,4 addition-elimination process.

Flash vacuum thermolysis of 5-substituted-4,4-diphenyl-3-oxa-1-azabicyclo[3.1.O]hexan-2- ones. A new route to quinolines.

Abstract Thermolysis of bicyclic carbamates produces quinoline derivatives good yields. A two step reaction is described.

Synthesis of monofluorinated compounds from methallyl chloride

Abstract Monofluorinated organic compounds gain an important position as biologically active substances or intermediates for synthesis of such compounds. However, the selective introduction of one fluorine substituent is sometimes difficult. Triethylamine tris-hydrofluoride (Et 3 N,3HF) in combination with different electrophiles are effective systems for monofluorination of olefins [1–3]. The halofluorination [1] of methallylchloride ( 1 ) gives mainly the corresponding Markovnikov addition products 2 and some traces of anti-Markovnikov orientated compounds 3 , while the bromofluorination of allyl chloride gave both regioisomers in a 4:1 ratio [4]. When using the combination dimethyl(methylthio)sulfonium tetrafluoroborate (DMTSF)/ Et 3 N,3HF [2] a mixture of mainly 2 (Xue5fbSMe), some 3 (Xue5fbSMe) and some amount of 4 (Rue5fbMe) has been isolated. The fluorosulfenylation, however, was not realized using phenylsulfenyl chloride in combination with Et 3 N,3HF; 1,3-dichloro-2-methyl-2-phenylthio-propane ( 5 ) was formed which is rearranged to 4 (Rue5fbPh) using Olahs reagent (−78°C to 0°C) or Et 3 N,3HF (16h, 60°C). Treatment of 5 with AgF in dichloro-methane at −30°C gave the desired fluorinated compound 2 (Xue5fbSPh).