Stereoselective synthesis asymmetric fluorination

ASYMMETRIC FLUORINATION METHODS APPLICATION IN THE STEREOSELECTIVE SYNTHESIS OF FLUORINATED DRUGS... 

ASYMMETRIC FLUORINATION METHODS APPLICATION IN THE STEREOSELECTIVE SYNTHESIS OF FLUORINATED DRUGS Electrophilic fluorination by means of chiral [N-F] reagents... 

Asymmetric Fluorination Methods Application in the Stereoselective Synthesis of Fluorinated Drugs... 

Oppolzefs chiral auxiliary,6 (-)-2,10-camphorsultam, is useful in the asymmetric Diels-Alder reaction,3 4 and for the preparation of enantiomerically pure p-substituted carboxylic acids7 and diols,8 in the stereoselective synthesis of A2-isoxazolines,9 and in the preparation of N-fluoro (-)-2,10-camphorsultam, an enantioselective fluorinating reagent.10... 

Bravo and co-workers report asymmetric syntheses of fluoroalkylamino compoimds via chiral sulfoxides and the stereoselective synthesis of p-fluoroalkyl-p-amino alcohol units using chiral sulfoxides and the Evans aldol reaction. Begde and colleagues discuss the stereoselective and enantioselective synthesis of trifluoromethyl amino alcohols and fluoroalkyl isoserinates. Hoffman reports the aysmmetric fluorination of a-aminoketones, while... 

Fluorine has also been introduced onto the E ring. For instance, both epimers of 20-fluorocamptothecin, where the fluorine atom replaces the 20-hydroxyl, have been prepared by total synthesis via stereoselective fluorination with DAST of the (K) and (S) a-hydroxylactone precursors (Figure 4.53). An asymmetric... 

A wide range of fluorinated compounds are applied as pharmaceuticals and agrochemicals. Several stereoselective methods are used for synthesis of optically active molecules bearing a C-F bond at the stereogenic carbon atom [72, 73]. These are mainly based on diastereoselective fluorination of chiral molecules or enantioselective alkylation of fluoroorganic compounds. Asymmetric introduction of a fluorine... 

It should be noted that the related imine-oxaziridine couple E-F finds application in asymmetric sulfoxidation, which is discussed in Section 10.3. Similarly, chiral oxoammonium ions G enable catalytic stereoselective oxidation of alcohols and thus, e.g., kinetic resolution of racemates. Processes of this type are discussed in Section 10.4. Whereas perhydrates, e.g. of fluorinated ketones, have several applications in oxidation catalysis [5], e.g. for the preparation of epoxides from olefins, it seems that no application of chiral perhydrates in asymmetric synthesis has yet been found. Metal-free oxidation catalysis - achiral or chiral - has, nevertheless, become a very potent method in organic synthesis, and the field is developing rapidly [6]. 

Oppolzer s camphor sultam, a well known chiral auxiliary, has been applied to the asymmetric synthesis of chial fluorine-containing amino acids <07OL2513>. Photoinduced addition of perfluoroalkyl iodides 189 to /V-acyloylcamphorsultam 188 in the presence of an aqueous solution of sodium sulfite provides alkyl iodides 190 with moderate to good stereoselectivities. Azide displacement with the major diastereomer of 190 proceeds with inversion of configuration. Subsequent removal of the sultam auxiliary and hydrogenation of the azide afford the chiral fluorine-containing amino acid 192. 

The current review is of necessity selective. Over the two year period covered, there has been impressive advances in several areas of P(V) chemistry. For example, biological aspects of quinquevalent phosphorus acids chemistry continue to increase in importance. A wide variety of natural and unnatural phosphates including inositols, lipids, some carbohydrates and their phospho-nates, phosphinates and fluorinated analogues has been synthesized. Special attention has been paid to the synthesis of phosphorus analogues of all types of amino acids and some peptides. Numerous investigations of phosphate ester hydrolysis and related reactions continue to be reported. Interest in approaches to easier detoxification of insecticides continues. A number of new and improved stereoselective synthetic procedures have been elaborated. The importance of enantioselective and dynamic kinetic asymmetric transformations is illustrated in many publications. 

Many other examples of stereoselective fluorinations with glycosides41, benzylic epoxy alcohols42, sterols43, and androstanols44 have been published. Asymmetric synthesis via heterocyclic intermediates is described for the fluorination of the chiral bislactim ether adduct of ketones45. 

Wang and co-workers developed an elegant catalytic asymmetric 1,3-dipolar cycloaddition of azomethine ylides with low reactive fluorinated imines as the dipolarophiles catalyzed by Cu(MeCN)4BF4/PPFOMe complex for the synthesis of 2,4-frans-fluorinated imidazolidines (Scheme 25) [45]. This catalytic system exhibited high reactivity, excellent stereoselectivity, and broad substrate scope. 

An alternate strategy is to use asymmetric induction by a preexisting chiral center in the substrate to direct the fluorination step. This approach has not been widely employed and the best results are those of Enders who reported Aat scalemic a-silyl ketones can be stereoselectively fluorinated at the a -position.(7) After desilylation, a-fluoro ketones can be obtained in high ee s for cyclic systems. Unfortunately, open chain systems give poorer results. In this symposium Davis has reported recent results using a chiral auxiliary as a stereocontrol element for the synthesis of a-fluoro esters in high enantiomeric purity.(8)... 

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