Reagent chirality effect

This methodology was further expanded to study the effect of including a third chiral substrate in the reaction mixture. In this manner, a reagent chirality effect (RCE) could be calculated as [115] ... 

Several reagents will effect the aziridination of alkenes directly, for example, electrophilic alkenes react with diphenylsulfilimine (1) in good yield, with the elimination of diphenyl sulfide (Scheme l). A similar reaction using the chiral sulfilimine (R)-(-t-)-(3) gives product (2 96%) as the (2R.3S) form shown (64%). accompanied by the enantiomer (32%). Cephalosporin substrates (4) react with achiral (1) to give pn ucts (5), as single diastereoisomers in 52-63% yields. ... 

In this context it is worth noting that neither the titanium(IV) tartrate catalyst nor other metal catalyst-alkyl hydroperoxide reagents are effective for the asymmetric epoxidation of unfunctionalized olefins. The only system that affords high enantioselectivities with unfunctionalized olefins is the manganese(III) chiral Schiff s base complex/NaOCl combination developed by Jacobsen [42]. There is still a definite need, therefore, for the development of an efficient chiral catalyst for asymmetric epoxidation of unfunctionalized olefins with alkyl hydroperoxides or hydrogen peroxide. 

There appear to be no examples of intramolecular ene reactions with carbonyl groups where absolute stereochemical control is dictated with a removable chiral auxiliary, and only one example with an external chiral agent. In this case, the chiral zinc reagent 4 effected practical levels of control with 3,3,7-trimethyl-6-octenaI106. 

This method relies on the chemical transformation of a racemate in which one of the enantiomers forms a product more rapidly than the other. The very first kinetic resolution of enantiomers was described by Pasteur [65]. This was the resolution of tartaric acid by fermenting yeast. Later, it was found that not only enzymes but also other chiral inductors such as chiral reagents, chiral catalysts, solvents or polarized light beam may effect kinetic resolution. It is important to note that the interaction time must be carefully controlled in kinetic resolution. The reaction has to be stopped at some point short of 100% conversion. Otherwise, both enantiomers of the starting material will be converted into the product, and no resolution is obtained. The slower interacting enantiomer can be obtained in an enantiomeri-cally enriched or even pure form. The product of a kinetic resolution may be either chiral or achiral. 

These schemes show how complex a synthetic project can become in order to supply a new dmg. The synthetic route outlined in these two schemes is characterized by a large number of steps, a diversity of reagents and effective chirality... 

When the achiral or chiral reagent approaches chiral ketone 10 from preferred diastereoface one, diastereomer is the prevailing product. Double asymmetric induction takes place when chiral ketone 10 is reduced by the chiral reagent or catalyst. As a result we can expect enhanced or lowered diastereoselectivity in comparison to the reaction with the achiral reagent. This is a consequence of the match or mismatch between the two chiral effects. 

If the amount of the sample is sufficient, then the carbon skeleton is best traced out from the two-dimensional INADEQUATE experiment. If the absolute configuration of particular C atoms is needed, the empirical applications of diastereotopism and chiral shift reagents are useful (Section 2.4). Anisotropic and ring current effects supply information about conformation and aromaticity (Section 2.5), and pH effects can indicate the site of protonation (problem 24). Temperature-dependent NMR spectra and C spin-lattice relaxation times (Section 2.6) provide insight into molecular dynamics (problems 13 and 14). 

The hydride-donor class of reductants has not yet been successfully paired with enantioselective catalysts. However, a number of chiral reagents that are used in stoichiometric quantity can effect enantioselective reduction of acetophenone and other prochiral ketones. One class of reagents consists of derivatives of LiAlH4 in which some of die hydrides have been replaced by chiral ligands. Section C of Scheme 2.13 shows some examples where chiral diols or amino alcohols have been introduced. Another type of reagent represented in Scheme 2.13 is chiral trialkylborohydrides. Chiral boranes are quite readily available (see Section 4.9 in Part B) and easily converted to borohydrides. 

Enantioselective processes involving chiral catalysts or reagents can provide sufficient spatial bias and transition state organization to obviate the need for control by substrate stereochemistry. Since such reactions do not require substrate spatial control, the corresponding transforms are easier to apply antithetically. The stereochemical information in the retron is used to determine which of the enantiomeric catalysts or reagents are appropriate and the transform is finally evaluated for chemical feasibility. Of course, such transforms are powerful because of their predictability and effectiveness in removing stereocenters from a target. 

Atroposelective cleavage of configurationally unstable lactone cycle in biaryl derivatives as effective route to chiral natural products and useful reagents 99S525. 

With few exceptions chiral Lewis acids are usually moisture-sensitive and require anhydrous conditions, but bench-stable aquo complexes such as [Cu(S,S)-t-Bu-box)(H20)2](SbF6)2 were found to promote the Diels-Alder reaction as effectively as the anhydrous copper reagent. 

A great advantage of catalyst 24b compared with other chiral Lewis acids is that it tolerates the presence of ester, amine, and thioether functionalities. Dienes substituted at the 1-position by alkyl, aryl, oxygen, nitrogen, or sulfur all participate effectively in the present asymmetric Diels-Alder reaction, giving adducts in over 90% ee. The reaction of l-acetoxy-3-methylbutadiene and acryloyloxazolidinone catalyzed by copper reagent 24b, affords the cycloadduct in 98% ee. The first total synthesis of ewt-J -tetrahydrocannabinol was achieved using the functionalized cycloadduct obtained [23, 33e] (Scheme 1.39). 

The chiral copper reagent 24 is an effective catalyst not only for intermolecular, hut also for intramolecular Diels-Alder reactions, as shown in the following schemes (Scheme 1.41, 1,42, 1.43). Synthetically useful octalin and decalin skeletons were synthesized in high enantio- and diastereoselectivity. The synthetic utility of this intramolecular Diels-Alder reaction has been demonstrated hy a short total synthesis of isopulo upone [23, 33d]. 

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