Fluorinating reagents chiral

Several oxaziridines related to (14) (eq 8) have been used, most notably in the enantioselective oxidation of sulfides to sulfoxides, of selenides to selenoxides, and of alkenes to oxiranes, It is also the reagent of choice for the hydroxylation of lithium and Grignard reagents and for the asymmetric oxidation of enolates to give a-hydroxy carbonyl compounds, - A similar chiral fluorinating reagent has also been developed, ... 

The enantioselective addition of a nucleophile to a carbonyl group is one of the most versatile methods for C C bond formation, and this reaction is discussed in Chapter 2. Trifluoromethylation of aldehyde or achiral ketone via addition of fluorinated reagents is another means of access to fluorinated compounds. Trifluoromethyl trimethylsilane [(CF SiCFs] has been used by Pra-kash et al.87 as an efficient reagent for the trifluoromethylation of carbonyl compounds. Reaction of aldehydes or ketones with trifluoromethyltrime-thylsilane can be facilitated by tetrabutyl ammonium fluoride (TBAF). In 1994, Iseki et al.88 found that chiral quaternary ammonium fluoride 117a or 117b facilitated the above reaction in an asymmetric manner (Scheme 8-42). 

The fluorination of enolates of ketone, amide, or hydrazone bearing a chiral auxiliary (SAMP, Evans oxazolidine) with nonchiral fluorination reagent (A-fluoro sulfonimides, A-fluoropyridine) occurs with excellent diastereoselectivities. ... 

Until recently the electrophilic fluorination of enolates and carbanions was difficult because many of the procedures employed corrosive materials or reagents that were not readily accessible. Progress in the fluorination of carbanions and enolates with chiral sultam reagents... 

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... 

Hydrogenation of 2,2,2-trifluoroacetophenone and its derivatives with a mixture of trans-RuCl2[(S)-xylbinap][(S)-daipen] and (CH3)3COK in 2-propanol gives the S alcohols quantitatively with a high optical purity (Scheme 1,64) [258]. Unlike with many chiral borane reagents [264], the sense of enantioface discrimination is the same as in hydrogenation of acetophenone. The electronic effects of 4 -substituents on the enantioselectivity are small. These chiral fluorinated alcohols are useful as components of new functionalized materials [265]. 

Tunoori, A. R., White, J. M., Georg, G. I. A One-Flask Synthesis of Weinreb Amides from Chiral and Achiral Carboxylic Acids Using the Deoxo-Fluor Fluorinating Reagent. Org. Lett. 2000, 2, 4091-4093. 

Recent advances in the syntheses of fluorinated amino acids have been summarized on the basis of the strategies for creating chiral centers in target amino acids (1) enantioselec-tive, (2) diastereoselective, and (3) racemic syntheses. Remarkable progress in fluorinating reagents and fluoro-functionalization methodologies the commercial availability of... 

A variety of highly enantioselective chiral N-F fluorinating reagents derived from Cinchona alkaloids were developed for the direct enantioselective fluorination of C—H acidic substrates (for details, see Chapter 6). Simultaneously, metal-catalyzed... 

Although enantioselective electrophilic fluorination can be achieved by use of a variety of chiral NF-reagents [204], enantiomeric excesses (ee) are only moderate and far lower than expected for real electrophilic addition. It might be speculated that the reason lies in the specific mechanism of electrophilic fluorination in general - the electron-transfer which presumably precedes fluorine transfer results in a short-lived radical intermediate which is configurationally unstable and can race-mize. 

Scheme 2.92 Uncharged chiral electrophilic fluorination reagents of the first generation N-fluoro camphorsultams 7a-7d [181a] and N-fluorosultam 8 [205].

Since the first asymmetric reduction of ketones with chiral borohydrides by Itsuno et al. [ 1 ], a number of studies on the asymmetric reduction of ketones with chiral borane reagents have been demonstrated [2]. Corey s oxazaborolidines are some of the most successful reagents [3 ]. The effect of fluorine substituents was examined in the asymmetric reduction of acetophenone with LiBH4 by the use of chiral boronates (73) obtained from substituted phenyl boronic acid and tartaric acid [4]. Likewise, 3-nitro, fluorine, and trifluoromethyl groups on the 3- or 4-position provided enhanced stereoselection (Scheme 5.20). 

Chiral shift reagents are also tris jS-diketonates based on d-camphor as the chiral moiety. Whitesides and Lewis (1970) introduced the tm[3-(rerf-butyl-hydroxy-methylene)-d-camphorato] europium. It is more soluble in organic solvents than Eu(dpm)3 with otherwise similar chemical properties. Fraser et al. (1971) prepared a fluorinated derivative anticipating advantages similar to those of R(fod)3 relative to R(dpm)3. Indeed their fWs[3-(heptafluoropropyl hydroxy-methylene)-d-camphorato] europium induces larger chemical shift differences between enantiomers in most of the cases. Even larger differences were obtained with fn. 5[3-trifluoromethyl-hydroxymethylene)-d-camphorato] europium (Goer-ing et al., 1971). 

Aliylboration of Fluorinated Aldehydes with Chiral Borane Reagents... 

Only a few enantioselective approaches to optically active 2,2-difluoro-3-hjrdroxy esters, key S)mthetic interme ates for a variety of important chiral fluorinated molecules, have been reported. Braun et al and Andrds et al. have independently reported that the Reformatsky reagents generated from bromodifluoroacetates react with aromatic aldehydes in the presence of stoichiometric amounts of chiral amino alcohols such as iV-methylephediine to afford the corresponding desired aldols in good optical yields (22,23). However, these methods are not catalytic, and the decrease in quantity of the chiral ligands dramatically suppresses the enantioselectivity. Thus, we became very interested in developing an unprecedented catalytic asymmetric aidol reaction of difluoroketene silyl acetals promoted by chiral Lewis acids. 

The use of a C-8 BINOL derivative (142) as a chiral anionic phase-transfer catalyst in a nonpolar solvent allowed the enantioselective fluorination of enamides (139) using Selectfluor (140) as the fluorinating reagent (Scheme 48). The authors demonstrated that a wide range of stable and synthetically versatile a-(fluoro)benzoylimines (141) could be readily accessed with high enantioselectivity (82-99% ee). ... 

Fluorinations of enolates with chiral reagent D (Table 3a) give moderate degrees of enantiomeric excess [671 (equation 43). 

Catalytic enantioselective fluorination has recently emerged. Both organocatalysis and metal catalysis have been successfully developed. Chiral N-F reagents have been prepared or formed in situ starting form a chiral amine derivative and a classical N-F reagent vide supra)P These reagents allow the enantioselective fluorination of... 

Asymmetric fluorination of the lithium enolate derived from tetralone 307 has been achieved with several new chiral A-fluoro-l,2-benzothiazine reagents (Scheme 44) <2000JOC7583, 2000CPB1954, see also 1999JFC(97)65>. For instance, sulfonamides 149 and 150 afford the opposite enantiomers of fluoroketone 308 in up to 79% yield and 62-70% ee. 

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