Two birds, one stone! The first kinetic resolution of allyl fluorides was achieved by the development of an organocatalyzed enantioselective allylic trifluoromethylation. Two kinds of chiral fluorinated compounds, which incorporate C*F and C*CF3 units, respectively, can thus be accessed by a single transformation.

Organic base-catalyzed reaction of (S)-N-tert-butanesulfinyl (3,3,3)-trifluoroacetaldimine with dialkyl malonates was found to be effective for synthesis of both (S,S(S)) and (R,S(S)) β-aminomalonates in high yield with good to excellent diastereoselectivity (76-98% de). The products of this Mannich reaction provide direct access to β-trifluoromethyl-β-alanine of either (R) or (S) absolute configuration.

Inorganic as well as organic base catalysis was found to be effective for diastereoselective Mannich additions of malonic acid derivatives to (SS)-N-(tert-butanesulfinyl)-3,3,3-trifluoroacetaldimine. In the presence of catalytic amounts of inorganic bases, n-BuLi or DMAP, the reaction gives the corresponding (R,SS)-β-aminomalonates in good yield and with diastereoselectivity up to 9/1 dr. In contrast, phosphazene bases favour the formation of the (S,SS)-diastereomer with selectivities as high as 99/1. Simple choosing of an appropriate base catalyst for the Mannich addition reaction allowed us to obtain enantiomerically pure (R)- or (S)-configured 3-amino-4,4,4-trifluorobutanoic acids after hydrolysis and decarboxylation of the corresponding β-aminomalonates.

Scheme 1. Kinetic resolution of MBH-type allyl fluorides 1 by enantioselective fluoroalkylation through CÀF bond activation/cleavage.

S‐((Phenylsulfonyl)difluoromethyl)thiophenium salts were designed and prepared by a triflic acid catalyzed intramolecular cyclization of ortho‐ethynyl aryldifluoromethyl sulfanes. The thiophenium salts were found to be efficient as electrophilic difluoromehtylating reagents for introduction of a CF2H group to sp3‐hybridized carbon nucleophiles such as of β‐ketoesters and dicyanoalkylidenes. The (phenylsulfonyl)difluoromethyl group can be readily transformed into CF2H under mild reaction conditions. Enantioselective electrophilic difluoromethylation was also achieved in the presence of bis(cinchona) alkaloids.

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Die erste kinetische Racematspaltung von Allylfluoriden wurde durch eine enantioselektive allylische Trifluormethylierung realisiert, die von Bis(chinaalkaloiden) katalysiert wird, wie N. Shibata et al. in der Zuschrift auf berichten. Zwei chirale fluorierte Verbindungen, die C*‐F‐ bzw. C*‐CF3‐Einheiten enthalten, können somit durch eine einzige Umsetzung erhalten werden. Gemälde: “Mori” (“Wald”) von Mami Shibata; der Weg durch den Wald kann zu etwas Spannendem führen.

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