asymmetric catalysis · electrophilic substitution · fluorinated substituents · fluorinationThe CÀF bond is a fundamental unit of organic chemistry, and its introduction into organic compounds has been widely deployed to optimize the properties of performance materials.[1] Important contemporary applications are in organic materials such as liquid crystals for display technologies, [2] the refinement of catalysts for asymmetric transformations, [3] as well as the important role of strategic fluorination for lead optimization in the pharmaceuticals sector.[4] Although fluorine is very often found on aromatic rings in, for example, pharmaceutical and agrochemical products, the enantioselective introduction of the C À F bond at a stereogenic center has emerged as a clear goal in organic chemistry ever since the first asymmetric fluorination reagents, N-fluorocamphorsultams 1 a, b, were reported by Differding and Lang [5] in 1988 (Scheme 1).There are obvious advantages in medicinal chemistry in replacing hydrogen with fluorine at metabolically vunerable carbon atoms and at enolizable centers in drugs, to lengthen in vivo half-lives. The quest for methods to mediate the introduction of the C À F bond with high enantioselectivity and with catalytic efficiency has been intense, and successes have been emerging rapidly as illustrated by related Highlights in 2006 [6,7] and in other recent reviews. [8][9][10] The major focus in asymmetric C À F bond formation has involved catalytic enolate/a-carbonyl fluorination of amides, b-cyano-, b-nitro-, and b-keto esters, as well as malonates. In 2005 there were a flurry of papers reporting the successful asymmetric fluorination of aldehydes using pyrrolidine or imidazolidinone organocatalysts in combination with electrophilic fluorinating reagents.[11] This progress has recently been reviewed in a Highlight.[6] Developments in asymmetric fluorination were slow for a decade after the discovery of the N-fluorosultams 1 a, b, [5] but subsequent progress has been rapid and impressive, particularly in using selectfluor (2) and N-fluorodibenzenesulfonimide (NFSI, 3) as electrophilic fluorine-transfer reagents for catalytic processes. The first efficient enantioselective fluorinations used reagents derived from cinchona alkaloid, which were independently discovered in 2000 in the laboratories of Cahard [12] and Shibata.[13] These protocols demonstrated high enantioselectivities (up to 91 % ee) but with stochiometric reagents. Catalytic fluorinations using selectfluor/NFSI as transfer reagents were demonstrated; however, they were not efficient.Asymmetric Lewis acid based catalysts also emerged in 2000.[13] Hintermann and Togni were the first to demonstrate such fluorination reactions, [14] using taddol-titanium complexes in combination with selectfluor to mediate the afluorination of b-keto esters. Such an approach has evolved to the present, in that chiral ligand-metal complexes have been discovered which can now mediate catalytic and highly enantioselective fluorination protocols. This ...

SummaryA three step route to single diastereoisomers of the vicinal trifluoromethyl motif is described. The route starts from either syn- or anti-α,β-epoxy alcohols and takes a direct approach in that each of the three steps introduces a fluorine atom in a regio- and stereo-specific manner. Starting from either the syn- or the anti-α,β-epoxy alcohol, stereospecific reactions generate two separate diastereoisomeric series of this motif. The route is a significant improvement on an earlier six step strategy.

Eine Methode wird erwachsen: Seit der Entwicklung der ersten asymmetrischen Fluorierungsreagentien 1988 ist die enantioselektive Einführung einer C‐F‐Bindung an einem stereogenen Zentrum ein wichtiges Forschungsziel in der organischen Chemie. Aktuelle Ergebnisse zur enantioselektiven Fluorierung von Malonaten (siehe Schema) dokumentieren den bereits guten Stand heutiger Fluorierungsmethoden. NFSI=N‐Fluordibenzolsulfonimid.

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