Stereoselectivity, factors

Stereoselection factors have been determined according to Kagan s equa-tion[6]. 

Tab. 7.3. Kinetic resolution of 5-substituted 2-cyclohexenones 53-56 according to Scheme 7.15 (s stereoselectivity factor).

Planar chirality is a valuable feature of the ferrocene chemistry (Chart 2B,C) (205). This unnatural chirality type has attracted attention of several groups. Sadeghi and co-workers have demonstrated that the planar chiral ferrocenes are recognized by cytochrome c peroxidase (206). The rate constants for the oxidation of R and S enantiomers by the wild type enzyme equal 2.9 x 106 and 1.6 x 106 M 1 s respectively. Interestingly, the enantioselectivity inverts for the aspartate 34 for lysine mutant and the rate constants become equal to 5.9 x 106 and 14.8 x 106 M-1 s-1, respectively. The discrimination of planar chiral ferrocenes is the case, but the stereoselectivity factors are lower than 3. 

In some cases MIPs can reach stereoselectivity factors of more than four,... 

The question remains of why our double racemic reaction shows net diastereoface selectivity of >49 1. It might be that we have been too conservative in selecting stereoselectivity factors. For example, there is a trend that the enolate used shows higher... 

Uemura et al. found that the combination Ti(OPr%/binaphthol/water in ratio 1 2 >10 acts as a catalyst for oxidation of aryl methyl sulfides into the corresponding sulfoxides by Bu OOH (see also Section 1.4.1) [159]. A mechanistic study showed that the titanium complex was a sulfoxidation catalyst (initial ee -50%) as well as a catalyst for the overoxidation into sulfones, with an enhancement of the ee of the residual sulfoxides (because the minor sulfoxide enantiomer is preferentially oxidized). In a subsequent paper, the authors reported the kinetic resolution of racemic aryl methyl sulfoxides by the same catalyst [160]. A stereoselectivity factor s of 2.6 was calculated for the kinetic resolution of racemic methyl p-tolyl sulfoxide. For example, methyl p-tolyl sulfoxide (<99% ee) could be recovered from oxidation at about 75% conversion. Using partially resolved l,l -binaphthol, a positive nonlinear effect was established. 

Equation 2.1 simplifies into Equation 2.2 by elimination of time t and taking r/ S Kel s (stereoselectivity factor). 

By using the values from Equation 2.5, Equation 2.3 gives the stereoselectivity factor s that may be transformed into Equation 2.6. 

In enzymatic reactions on a racemic mixture, Sih et al. have proposed to characterize the enantioselectivity of the process by the rate ratio E (for enantiomeric ratio) [24]. It is very similar to the stereoselective factor s and led to an equation similar to Equation 2.6. For details, see Chapter 7. 

Davies et al. [64] could resolve tert-butyl ( )-3-methylcyclopentene-l-carboxylate 77 through conjugate addition of lithium dibenzylamide 78. It was shown that the lithium dibenzylamide adds preferentially to the face of the double bond anti- to the 3-methyl substituent. Reaction of ( )-77 with ( )-78 allowed the evaluation of the diastereoselectivity of the process which is also the stereoselectivity factor s, provided there is no non-linear effect. Indeed, treatment of ( )-77 with 0.7 equiv of (S)-78 at -78 °C for 3 h, followed by quenching gave, at 51% conversion, a mixture of stereoisomers with 79 as the major one, and recovered (S)-77 in 99 0.5% ee. 

When a mixture of diastereomers reacts with a chiral or achiral reagent, it involves two competitive reactions. The rate laws are very similar to the one estabhshed for the KR (see Section 2.1). The stereoselectivity factor is the relative rate constants of reaction of the two diastereomers. One of the two diastereomers will be destroyed more slowly than the other and will be recovered with some diastereomeric excess (de jj ) that increases with conversion. Equation 2.6 applies by replacing ee j by de j. ... 

Precatalysts 41a-c and 44 were activated with MAO and tested for kinetic resolution. Tetradecane was used as a solvent for these polymerizations at 25 °C. Kinetic resolution was reported by using stereoselectivity factors, or values, where s = (rate of fast reacting enantiomer)/(rate of slow reacting enantiomer). Experimentally, s may be calculated by using the following equation s = ln[(l -c)(l -ee)]/ln[(l - c)(l-fee)], where ee is the enantiomeric excess of the recovered olefin and c is the fraction conversion. If no kinetic resolution is achieved, s = 1. The authors assayed the fraction conversion, c, by gas chromatography (GC) analysis of two aliquots for each polymerization run (1) an aliquot removed immediately before the start of polymerization (i.e., immediately before the addition of zirconocene catalyst) and (2) an aliquot removed after the desired conversion was reached in all cases, tetradecane was used as the internal standard. 

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