Enolates asymmetric electrophilic fluorinations

Shibata successfully adapted the asymmetric transfer fluorination to cyclic silyl enol ethers, cyclic allyl silanes and oxindoles, illustrated in Schemes 13.1-13.3, as a catalytic method (Scheme 13.6) [16]. Similar reaction conditions were identified for all three substrates, including the use of stoichiometric NFSI as the electrophilic fluorine source and a stoichiometric inorganic base additive. It was observed that bis-Cinchona alkaloid (DHQ)2PHAL was best for cyclic silyl enol ethers (X = 0), (DHQ)2PYR (Scheme 13.2) was best for cyclic allyl silanes (X = CH2), while (DHQD)2AQN was best for oxindoles. A similar method was applied to cyclic enol ethers, providing products in modest ee s [17]. 

From a non-c ohydrate precursor, Davis and Qi achieved the asymmetric synthesis of 2-deoxy-2-fluoro- iylo-D-pyranose (9) (Figure 7) and 2-deoxy-2-fluoro-lyxo-L-pyranose (13). TTie key reaction was the highly diastereoselective fluorination of a chiral enolate using the electrophilic fluorinating agent, N-fluoro(benzenesulfonimide) (NFSi). In another study by Davis (14), the use of a chiral oxazolidinone adjuvant and fluorination with NFSi led to the chiral fluorohydrin 10 (>97% ee), which was oxidized by the Dess-Martin periodinane procedure to the non-racemic a- fluoroaldehyde 11 (94% ee). Conversion of 11 in four steps provided l,2,3-tri-0-acetyl-4-deoxy-4-fluoro-D-arabinopyranose (12) as a 1 1 mixture of anomers which could not be separated by flash chromatography. 

A -Fluoro-dihydrobenzo[l,2-i isothiazole is an efficient agent for electrophilic asymmetric fluorination of enolates <1999JOG5708>. A -Fluoro-2,10-camphorsulfonamide 237 (see Section 4.05.6.4.2) is a good asymmetric reagent for a-fluorination of ketones <1998JOG9604>. 

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