No abstract

Chiral-anion phase-transfer catalysis (PTC) has been applied towards the enantioselective fluorocyclization reactions of 1,3-dienes. The method affords unprecedented fluorinated benz[f]isoquinoline and octahydroisoquinoline products in high yields and up to 96 % ee. New fluorinated amine reagents outperformed Selectfluor in the desired transformation.

Effective CF(3) transfer: Various electron-rich nitrogen heterocycles (pyrazoles, triazoles, and tetrazoles) can be directly N-trifluoromethylated by a hypervalent iodine reagent in an efficient manner. The optimized procedure, which includes an in situ silylation of the substrate followed by an acid-catalyzed CF(3) transfer, provides ready access to a series of new and previously challenging or inaccessible NCF(3) compounds.

The unique features the trifluoromethyl group imparts to pharmaceuticals, crop-protection agents, and functional materials emphasize the necessity to design and develop new reagents and methods for the direct trifluoromethylation of a wide range of organic substrates. Electrophilic trifluoromethylation, that is, the reaction of a suitable reagent capable of formally transferring an intact CF 3 + unit, has been shown to be one of these methods.[1] However, despite the availability of several such effective reagents, the electrophilic trifluoromethylation of hard nucleophiles, for example, oxygen-or nitrogen-centered ones, remains challenging. In particular, the formation of a N À CF 3 bond by such a reaction is still extremely rare. In fact, the NCF 3 unit is usually constructed by the interconversion of suitable functional groups. Thus, fluorination of N-formylamines, [2] thiuram sulfides, [3] isocyanates, [4] and trichloromethylamines, [5] the reaction of secondary amines with CBr 2 F 2 and tetrakis(dimethylamino)ethylene, [6] and the electrochemical fluorination of alkylamines [7] constitute the still relatively modest set of methods. Of these, the most frequently used approach is the oxidative desulfurization-fluorination of dithiocarbamates first described for the generation of NCF 3 groups by Hiyama and Kuroboshi.[8]The single, still very recent report of a direct trifluoromethylation at nitrogen is due to Umemoto and co-workers.[9] They describe the direct N-trifluoromethylation of amines, anilines, and pyridines under very mild conditions achieved with in situ generated and thermally unstable O-(trifluoromethyl)dibenzofuranium salts (corresponding reactions of alcohols and phenols are also known). However, this type of reagent suffers from several shortcomings. The active CF 3 source is obtained by photochemical decomposition of diazonium salts at very low temperature, and the synthesis requires several steps including the construction of a CF 3 O-aryl moiety. It is therefore likely that this methodology will not replace the corresponding functional-group interconversions in the near future.We have shown that a new generation of readily accessible trifluoromethylation reagents based on hypervalent iodine, such as compounds 1 and 2 (Scheme 1), display the desired reactivity towards a number of C-, S-, P-, and O-centered nucleophiles. Despite their purported soft nature, reagents 1 and 2 do trifluoromethylate alcohols and sulfonic acids upon activation with Lewis [10] and Brønsted acids, [11] respectively, thus significantly expanding their application range.During a recent investigation of the direct electrophilic trifluoromethylation of heteroarenes [12] using reagent 1 and catalytic amounts of bis(trifluoromethanesulfonyl)imide (HNTf 2 ) in acetonitrile, we surprisingly found that benzotriazole (3) is converted to the corresponding N-substituted N-trifluoroimidoyl derivative 4, as shown in Scheme 2. The generation of compound 4 corresponds to a novel Rittertype [13] reaction during which a new NÀCF 3 bond...