Enantioselective synthesis electrophilic fluorination

Asymmetric electrophilic fluorination has already found application in medicinal chemistry. For example, the enantioselective synthesis of a fluorooxindole, Maxipost (BMS-204352), has been reported. This compound is an effector for opening calcium channels and is currently in development for the treatment of cerebral ischemia (Figure 2.5). ... 

Enders D, Potthoff M (1997) Regio- and enantioselective synthesis of alpha-fluoroketones by electrophilic fluorination of alpha-silylketone enolates with N-fluorobenzosulfonimide. Angew Chem Int Ed Engl 36 2362-2364... 

Enders D, Faure S, Potthoff M, Runsink J (2001) Diastereoselective electrophilic fluorination of enantiopure a-silylketones using N-fluoro-benzosulfoni-mide regio- and enantioselective synthesis of a-fluoroketones. Synthesis 2001 2307-2319... 

An interesting catalytic diastereo- and enantioselective tandem transformation via Nazarov cyclization /electrophilic fluorination has been efficiently promoted by a (/ ,/ )-Ph-BOX-Cu(II) complex to afford fluorine-containing 1-indanone derivatives with two new stereocenters with high diastereoselectivity trans/cis up to 49/1) and moderate-to-high enantioselectivities (up to 95.5% ee) (Scheme 44.24). This catalytic enantioselective tandem transformation can be used for synthesis of organofluorine compounds with adjacent carbon- and fluorine-substituted tertiary and quaternary stereocenters. " ... 

In 1999, both enantiomers of the fluorinated analog were obtained using LiHMDS and perchloryl fluoride as an electrophilic source of fluorine in 71% yield. After several steps, the enantiomers were separated using chiral high-performance liquid chromatography (HPLC) and biologically evaluated. More recently, the first enantioselective synthesis of both enantiomers of thalidomide was described with the aid of a chiral [N-F]+ reagent obtained by combination of a cinchona alkaloid, dihydroquinine (DHQ), and... 

Mohar B, Sterk D, Ferron L, Cahard D. Enantioselective and diastereoselective synthesis of fluorinated dipeptides by late electrophilic fluorination. Tetrahedron Lett. 2005 46 5029-5031. 

Mohar B, Baudoux J, Plaquevent J-C, Cahard D. Electrophilic fluorination mediated by cinchona alkaloids highly enantioselective synthesis of a-fluoro- a-phenylglycine derivatives. Angew. Chem. Int. Ed. 2001 40 4214-4216. 

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