A novel reagent, [(oxido)phenyl(trifluoromethyl)-λ 4 -sulfanylidene]dimethylammonium tetrafluoroborate has been developed for the electrophilic trifluoromethylation of carbon nucleophiles. The reagent was designed as a trifluorinated version of a Johnson-type methyl-transfer reagent. The first

The enantioselective incorporation of fluorine into organic molecules has been extensively exploited because chiral functional groups with a CÀF unit have attractive properties for pharmaceutical and materials applications.[1] The first results on catalytic enantioselective fluorination were reported by Togni et al. in 2000 for the reaction of b-keto esters using Ti IV /TADDOL catalysts.[2a] Since then, several methods for the catalytic enantioselective fluorination of 1,3-dicarbonyl compounds and related substrates have been developed. [2,3] The enantioselective fluorination of aldehydes catalyzed by proline and its analogues is also a recent topic in this field.[4] However, a major limitation of this methodology is that ketones are poor substrates. Thus, the construction of compounds containing a chiral quaternary carbon center with a fluoro substituent remains problematic, with the exception of the examples reported by Jørgensen et al.[4e]In 2000 we developed combinations of cinchona alkaloids and Selectfluor, that is, N-fluoroammonium salts of cinchona alkaloids, as enantioselective fluorinating reagents, [5a] and similar reagents were also independently reported by Cahard et al.[6a] The advantage of these reagents is that a wide range of substrates including silyl enol ethers, 1,3-dicarbonyl compounds, lactones, oxindoles, dipeptides, and allyl silanes can be effectively fluorinated in a highly enantioselective manner.[6] The asymmetric fluoro semipinacol rearrangement of allylic alcohols is also induced by this combination. [6i] However, this methodology requires a stoichiometric amount of the cinchona alkaloid, and the catalytic version of the reaction has not been very successful.[7] Herein we disclose the first successful catalytic enantioselective fluorination based on cinchona alkaloids (Scheme 1). Allyl silanes and silyl enol ethers undergo efficient enantioselective fluorodesilylation with N-fluorobenzenesulfonimide (NFSI) and a catalytic amount of a bis-cinchona alkaloid in the presence of excess base to provide the corresponding fluorinated compounds with a F-substituted quaternary carbon center with enantioselectivities up to 95 % ee. Furthermore, we demonstrate that the methodology can be effectively extended to the catalytic enantioselective fluorination of oxindoles. The X-ray crystal structure of the biscinchona alkaloid dihydroquinine(2,5-diphenyl-4,6-pyrimidinediyl diether) ((DHQ) 2 PYR) is also disclosed for the first time.We started by attempting a catalytic version of the stoichiometric enantioselective fluorodesilylation of allyl silane 1 a described by Gouverneur et al.[6h] (Table 1). Using a catalytic amount of (DHQ) 2 PYR and 1.2 equiv of Selectfluor as the fluorination reagent in CH 3 CN at 0 8C, 1 a was converted to allylic fluoride 2 a in 46 % yield as a racemate (entry 1, Table 1). We assume that an initial transfer fluorination from Selectfluor to (DHQ) 2 PYR did not proceed since Selectfluor reacts more readily with allyl silane 1 a than with the cinchona alkaloid. We next u...

The catalytic, nucleophilic enantioselective trifluoromethylation reaction of both acyclic and cyclic aryl ketones using the Ruppert-Prakash reagent is now at hand, with an operationally simple procedure, based on the combination of ammonium bromide of cinchona alkaloids with TMAF. The procedure is reliable and general. Trifluoromethyl-substituted tetrasubstituted aryl alcohols have been synthesized in up to 94% ee.

The first catalytic enantioselective hydroxylation reaction of both 3-aryl and 3-alkyl-2-oxindoles using the DBFOX-Zn(II) complex, leading to pharmaceutically important chiral 3-hydroxy-2-oxindoles was described. The structure of oxidant was found to play an important role to increase the enantioselectivity. The methodology has successfully applied to the highly enantioselective hydroxylation of beta-keto esters using the DBFOX-Ni(II) complex.