Powerful probes for revealing the workings of biological systems can be prepared through the judicious replacement of hydrogen atoms with fluorine. [1] The C À F bond has a significant effect on the reactivity, stability, and bioavailability of molecules. [2] Thus, there is a strong demand for a wider availability of versatile fluorine-containing building blocks; enantiopure ones are particularly in demand. [3] The fluorinated amino acids [4] (F-AAs) impart unique properties when they were used in the modification of peptides and proteins in protein engineering. They are also ideal intermediates for drug-discovery programs and have found their way into drugs like Vaniqa (antineoplastic agent). [1] Fluorinated aamino acids [5] (F-a-AAs) are also well known as irreversible inhibitors of pyridoxal phosphate-dependent enzymes. Conversely, much less is known about fluorinated b-amino acids (F-b-AAs). [5b, 6] As they are potential precursors for b-lactams, various strategies for the stereoselective synthesis of b-AAs have been reported. [6,7] Among these, the most robust and powerful method is attributed to the asymmetric Mannich reaction, of which several organocatalytic versions have been developed over the past few years. [8, 9] However, the synthesis of F-b-AAs by using asymmetric Mannich reactions is still rare despite these developments. Furthermore, the synthetic route to a-fluorinated b-amino acids (a-F-b-AAs), particularly those containing chiral quaternary a-carbon center, is virtually unexplored. [10] Recently, we reported the bicyclic, guanidine-catalyzed [11] formation of asymmetric C À F bonds using a-fluoro-b-ketoesters as fluorocarbon nucleophiles in highly enantio-and diastereoselective conjugate-addition and Mannich reactions. [11d] Such a-fluoro-b-ketoesters have also recently been exploited by the groups of Lu, [12] Maruoka, [13] and others. [14] Catalytic enantioselective nucleophilic fluorination is not common, and the other successful example is the use of 1-fluoroA C H T U N G T R E N N U N G bis(phenylsulfonyl)methane (FBSM). Shibata, Toru, and co-workers have reported the use of this fluorocarbon nucleophile in palladium-catalyzed, allylic-replacement, [15a] Mannich-type, [15b] and Michael reactions with a,b-unsaturated ketones. [15c] This fluoronucleophile was also used by Prakash, Olah, and co-workers in Mitsunobu [16a] and Michael addition to chalcones. [16b] In our preliminary studies, we obtained excellent yield from the Mannich reaction between a-fluoro-b-ketoester 1 a and N-ethoxycarbonyl imine 2 a, although the enantio-and diastereoselectivities were moderate (Table 1, entry 1). Our experiences with bicyclic, guanidine-catalyzed, asymmetric reactions allowed us to predict that the catalyst system would respond well to changes in the steric properties of the substrates. Hence, we changed the N-ethoxycarbonyl imine 2 a to N-tert-butyloxycarbonyl (Boc) imine 2 b. The diastereoselectivity increased slightly, but the enantiomeric excess (ee) value decreased (Table 1, entry 2). We then worked on the a-fluoro-b-ketoester, and replaced the ester moiety with oxazolidinone, as it has an additional opportunity for hydrogen bonding due to the additional carbonyl groups. The lower reactivity of b-keto acetyloxazolidinone 1 b meant that the reaction with N-Boc imine 2 b had to be carried out at room temperature; a moderate ee value was obtained, but the diastereoselectivity was lost (Table 1, entry 3). How-[a] Y. Pan, Y.