Chirality, effect fluorines

Morpholinosulfur trifluoride is more thermally stable and therefore safer to handle than DAST and gives a slightly higher yield of the fluoride in the fluorination of cyclohexanol [95, ISO] Both solvent and conformational effects are pronounced in the fluorination of cyclohexanols [550] The chiral (S)-2-(methoxymethyl)pyr-rolidin-l-ylsulfur tnfluonde is an effective enantioselective fluorodehydroxylating agent [ISI]... 

Results for these CEBEs are presented in Table 1. As can be seen, for the carvone variants I-V the various substitutions have absolutely no effect at the carbonyl C=0 core, and are barely significant at the chiral center that lies between the carbonyl and substituent groups in these molecules. Only upon fluorine substitution at the tail (molecule VI) does the C=0 CEBE shift by one-half of an electronvolt the second F atom substitution adjacent to the C=0 in the difluoro derivative, VII contributes a further 0.6-eV shift. This effect can be rationalized due to the electron-withdrawing power of an F atom. Paradoxically, it is these fluorine-substituted derivatives, VI, VII, that arguably produce b curves most similar to the original carvone conformer, I, yet they are the only ones to produce a perturbation of the ground-state electron density at the C li core. This contributes further evidence to suggest that, at least for the C li... 

A very impressive example of the synthetic utility of this chemistry is the one-pot enantioselective double G-H activation reaction of 86 to generate chiral spiran 87 (Equation (73)).172 In this case, the phthalimide catalyst Rh2(enantiotopically selective aromatic C-H insertions of diazo ketoesters (Equation (74)).216 Moreover, dirhodium(n) tetrakisIA-tetrafluorophthaloyl- )-/ /-leucinate], Rh2(hydrogen atoms of the parent dirhodium(n) complex are substituted by fluorine atoms, dramatically enhances the reactivity and enantioselectivity (up to 97% ee). Catalysis... 

From this series of calculations it is noted that the gas-phase reactivity of TFDO is substantially greater than that of DMDO. This rate difference has been ascribed largely to the inductive effect of the CF3 group. Fluoro-substituted dioxiranes have also played a unique role in the chiral epoxidation of alkenes. Houk and coworkers96 have identified a novel stereoelectronic effect that increases the rate of epoxidation when the fluorine substituent is anti to the oxygen of the developing C=0 group in the TS for epoxidation. 

The biotransformation of organofluorine materials into optically active functionalized fluo-rinated materials along with a discussion on the effect of fluorine atom(s) during enantio-selective and/or diastereoselective transformations is described. The ability of microorganisms to discriminate between enantiomers is particularly important regarding resolution and asymmetric synthesis. Furthermore, the use of chiral fluorinated materials in the design and preparation of new types of biologically active materials is discussed. 

The Pummerer rearrangement has also been used to transform the 4-tolylsulfinyl group, which is an effective chiral auxiliary, into other functionalities via the aldehyde. Thus, chiral /> -(ben-7yloxy)-/J-(fluoroalkyl) sulfoxides 11 have been transformed into aldehydes 12 in a two-step process.7,8 The 3,3-difluoro-substituted aldehydes 12 can be converted directly into a variety of other functional groups without isolation. The chiral center at C2 is derived from the corresponding chiral / -oxo sulfoxide, which can be reduced diastereoselectively due to the presence of the chiral 4-tolylsulfinyl group.7,8 Diastereoselective reduction of fluorine-free fi-oxo sulfoxides has been intensively studied, especially in the laboratories of Solladie.9... 

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]. 

Takeuchi and coworkers have achieved the catalytic enantioselective protonation of a samarium enolate 45 in the THF/FC-72 [F3C(CF2)4CF3] biphasic system using a C2-symmetric chiral diol 5 (DHPEX) or a fluorinated chiral alcohol 6 as a catalyst and a fluorinated achiral alcohol 46 (Scheme 3) [11]. The fluorinated biphasic system was more effective than THF alone, and enantioselectivities near maximum values were obtained in the reaction. In addition, it was unnecessary to add the achiral alcohol 46 slowly to the reaction mixture. 

Most chiral organoboron Lewis acids reported to date are based on an organoborane that is attached to a chiral organic moiety such as a diol, aminoalcohol, or other readily available chiral substrates.Organoboron derivatives recently used as catalysts in enantioselective Diels-Alder reactions include the family of chiral acyloxyboranes (CAB) with (196) and (197) as representative examples and various cyclic boronic esters such as (198) and (199). An interesting system that combines the favorable Lewis acid properties of fluorinated arylboranes with a chiral Bronsted acid has been developed by Ishihara and Yamamoto. The Bronsted acid-assisted chiral Lewis acids (BLA) (200) was found to be highly effective in enantioselective cycloadditions of Q ,jS-enals with various dienes. The presence of the Bronsted acid functionality leads to significant acceleration of the reaction. 

In the development of chiral lithium amides which result in higher ee, the effect of a diverse set of substituents R and R in 38 was examined. It was shown that ee increases as the size of substituent R becomes bulkier, and also as the amount of fluorine in R increases. In THF, 38a occurs as a monomeric structure M-38a in either the presence or absence of HMPA. Fluorinated base 38b has also been shown to be monomeric in THF, consistent with structure M-38b where the fluorine atoms do not act as internal chelating ligands. In the presence of LiCl, the solution structure of labeled 38b was examined by Li and NMR in THF-ds- The Li- N coupling patterns showed that mixed dimer MD-6 was formed, as also illustrated with 38a. The absolute configuration of the products renders the OD-1 structure of transition state TS-1 most likely (Fig. 7) [58]. 

A chiral analog of DAST, (S)-2-(methoxymethyl)pyrrolidin-l-ylsulfur trifluoride [131], was prepared and studied to achieve enantioselection in the fluorination of chiral alcohols by double stereodifferentiation (Scheme 2.60). The desired effect was observed, but not to a preparatively useful extent. 

Synthesis of Phosphoric Acids and Their Derivatives. - A series of monoalkyl and dialkyl phosphorus acid chiral esters have been synthesised for use as carriers for the transport of aromatic amino acids through supported liquid membranes. The compounds acted as effective carriers but enantio-separation was at best moderate. A range of phosphono- and phosphoro-fluoridates have been prepared by treatment of the corresponding thio- or seleno- phosphorus acids with aqueous silver fluoride at room temperature (Scheme 1). In some cases oxidation rather than fluorination occurred. Stereospecifically deuterium-labelled allylic isoprenoid diphosphates, e.g. (1), have been synthesised from the corresponding deuterium-labelled aldehyde by asymmetric reduction, phosphorylation and Sn2 displacement with pyrophosphate (Scheme 2). ... 

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