Indoles, 4,5,6,7-tetrafluoro

The most convenient syntheses of tryptamines involve treatment of indole with aziridines. The reaction of indole (143) with aziridinium tetrafluoro-borate (144) afforded tryptamine (145) in 40% yield (Scheme 29). However, lack of regioselectivity in this reaction gives l-(2-aminoethyl)indole (146) as a by-product. 

Carbonyl compounds of the general formula C,Fb CH2-COR also form the basis of routes to 4,5,6,7-tetrafluorobenzo(6]furan (76a) and its 2-phenyl-derivative (76b) and to 4,5,6,7-tetrafluoro-l,2-diphenylindole (78) (Scheme 20).i36 Yields in cyclizations of this type increase with the size of the group R, probably as a consequence of the need for trans geometry in the intermediates involved [(75) and probably (77) an alternative, but less favoured, route to the indole has been suggested Alternative approaches to fluorinated... 

Alternative method for the synthesis of tetrafluoroindole was described in 1968. Ketone 133 was heated under reflux with aniline in the presence of anhydrous zinc chloride in order to prepare the Schiff base 134. However, the only product isolated was A-phenyl-4,5,6,7-tetrafluoro-2-methylindole 136 (<10 %). The yield of 136 was increased up to 47 % by the addition of aniline hydrobromide to the reaction mixture. Thus, the improved synthesis of indole 136 includes heating of the ketone 133, aniline hydrobromide, anhydrous zinc chloride and aniline under reflux for 2 h [53]. 

Copper-catalyzed Direct Phenylation of Indoles. The site-selective direct phenylation of an indole bearing a tetrafluoro-phenyl substituent has been achieved in 64% yield using diphenyUodonium triflate, Cu(OTf)2, and 2,6-di-tert-butylpyridine in dichloromethane (eq 11). This coupUng occurs selectively at the C3 position of the indole ring under copper-catalyzed conditions, with no phenylation occurring at the C2 position of the indole ring or on the tetrafluorophenyl substituent. ... 

Typical experimental procednre for BMS-204352 To a solution of l,4-diazabicyclo[2.2.2]octane (35 mg, 0.31 mmol) in THF (1 mL) was added 3-(5-chloro-2-methoxy-phenyl)-6-trifluoro-methyl-l,3-dihydro-indol-2-one (48 mg, 0.14 mmol) at 20°C. The mixture was stirred for 30 minutes, and then the temperature was cooled to —78 °C. lV-fluoro-2-naphtoylquininium tetrafluoro-borate (F-2NaphtQN-Bp4) (99.4 mg, 0.17 mmol) was dissolved in a mixture of 3-mL CH3CN/4=mL CH2Cl2and added over a period of 1 hour. The mixture was stirred overnight during that time temperature rise from -78 °C to 0°C and then quenched with 8mL of water. The aqueous phase was extracted with... 

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