Chiral auxiliaries electrophilic fluorination

Substituted 2-oxazolidones 165 are useful chiral auxiliaries for diastereoselective functionalization at the a-carbon of their amide carbonyl group. The a-fluoroaldehydes 166 were prepared by a series of reactions electrophilic fluorination of the corresponding oxazolidinone sodium enolates with AMluorobenzenesulfonimine reductive removal of the auxiliary with LiBH4 and Dess-Martin oxidation. The aldehydes are so unstable for isolation that they are converted with (R)-/ -toluenesulfinamide to /7-toluenesul(inimines 167, which are isol-able and satisfactorily enantio-enriched. Chiral sulfinimine-mediated diastereoselective Strecker cyanation with aluminum cyanide provided cyanides 168 in excellent diastereose-lectivity, which were finally derived to 3-fluoroamino acids 169 (see Scheme 9.37) [63]. 

A different approach to enantioselective electrophilic fluorination is the use of chiral auxiliary groups on the substrate this converts the problem into a diastereo-selective fluorination. The ground-breaking work in this field was done since 1992 by the Davis group [207], by fluorination of imide enolates modified by Evans oxazolidinone chiral auxiliary [208] using N-fluoro-o-benzenedisulfonimide (NFTh) as the electrophilic fluorination agent (Scheme 2.94). 

These reagents are used either in diastereoselective electrophilic fluorinations for which the stereoselectivity is directed intramolecularly by an enantiopure substrate, often of natural origin, or having a temporary attached chiral auxiliary or in enantioselective electrophilic fluorinations of achiral substrates with the aid of a chiral reagent or catalyst. 

We are now presenting examples of asymmetric electrophilic fluorinations controlled by covalently bound chiral auxiliaries that are removed after the stereoinduction step. The chiral auxiliary could be used stoichiometrically when initially bound to the substrate or in situ reacted with the substrate under catalytic conditions. In the first case, N-acy-loxazolidinones provided high levels of diastereoselectivity by selective approach of the fluorinating agent (typically, NFSI or NFOBS) from the less hindered face of the chiral... 

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