Degree of enantioselection

Initial studies on the Jacobsen-Katsuki epoxidation reaction identified conjugated eyelie and acyelic cw-disubstituted olefins as the class of olefins best suited for the epoxidation reaetion. " Indeed a large variety of c/s-disubstituted olefins have been found to undergo epoxidation with a high degree of enantioselectivity. 2,2"-Dimethylehromene derivatives are especially good substrates for the epoxidation reaetion. Table 1.4.1 lists a variety of examples with their corresponding reference. 

Barluenga et al. have described novel vinylcarbene complexes containing a cyclic BF2 chelated structure which temporarily fixes the s-cis conformation of the exocyclic C=C and Cr=C double bonds. These boroxycarbene complexes behave as dienophiles with 2-amino-l,3-butadienes in a remarkably regio- and exo-selective way. Moreover, high degrees of enantioselectivity are reached by the use of chiral 2-aminodienes derived from (S)-methoxymethylpyrrolidine [101] (Scheme 54). 

The degree of enantioselectivity of (Ipc)2BH is not high for all simple alkenes. Z-Disubstituted alkenes give good enantioselectivity (75-90%) but F-alkenes and... 

The advent of synthetic cannabimimetics with a high degree of enantioselectivity (Johnson, 1986 Little, 1988) paved the road for the identification of specific cannabinoid binding sites in rat brain (Devane, 1988). This discovery marked the onset of a revolution in the understanding of cannabinoid biology. 

The degree of enantioselective bias was improved shortly after this time. In 1971, Morrison et al. reported that the rhodium(I) complex [RhCl(NMDPP)3] (NMDPP= neomethyldiphenylphosphine) reduces ( )-/ -methylcinnamic and ( )-a-methylcinnamic acids with 61 and 52% ee, respectively (Scheme 1.9) [41]. NMDPP is a monodentate phosphine derived from (-)-menthol, and its asymmetry lies at carbon atoms. 

In these Heck reactions some degree of enantioselectivity (up to 83% ee) is achieved in the presence of (/ )-BINAP, although the yields of Heck products are often very low in the highest degree of enantioselectivity (e.g., 19% isolated yield at 83% ee) [93]. An example of a tandem Heck reaction is shown below involving the arylation of dihydropyrrole 132 with 1-naphthyl triflate (133) [92]. Complete chirality transfer is observed for the arylation of 134 to 135. 

Since the electroreduction of ketones shown in Scheme 29 has been well established [1-3, 12, 62-65], one more recent interest in the electroreduction of carbonyl compounds is focused on the stereo-selective reduction of ketones. For example, the diastereo-selective cathodic coupling of aromatic ketones has been reported. In the presence of a chiral-supporting electrolyte, a low degree of enantioselectivity has been found [66] (Scheme 30). 

The preferential formation of one stereoisomer over another in a chemical reaction. If the stereoisomers of concern are enantiomers then the term enantioselectivity is often used. The degree of enantioselectivity is usually expressed by the enantiomeric excess. If the stereoisomers of concern are diastereoisomers, then the term used is diastereoselectivity. It is quantitatively measured by the diastereoisomer excess. 

A major advantage of enzymes as catalysts is that they are capable of inducing very high degrees of enantioselectivity and, consequently, they are particularly useful in the synthesis of enanhomerically pure compounds. In cases where the enanh-oselectivity is less than optimum it can generally be improved using protein engineering techniques such as in vitro evolution [10]. Hence, in this chapter we shall be mainly concerned with the application of enzymatic cascade processes to the... 

High degrees of enantioselectivity have been observed when alkylzinc reagents react with aldehydes in the presence of chiral ligands.120 Among several compounds that have been used as ligands are exo - (dime th y I a m i no )no rb o rn c o I (A)121 122 123 124 and diphenyl(l-methyl-pyrrolin-2-yl)methanol (B) as well as ephedrine derivatives C and D. 

Chiral aminoalcohols both catalyze reactions of simple dialkylzinc reagents with aldehydes and also induce a high degree of enantioselectivity, even when used in only catalytic amounts. Two examples are given below. Indicate how the aminoalcohols can have a catalytic effect. Suggest transition states for the examples show which would be in accord with the observed enantioselectivity. 

One of the major goals set for tandem ylide formation-cycloaddition chemistry has been the application of enantioselective catalysis to form one product in preference to all others. It appears that these transformations must involve a catalyst associated ylide for some degree of enantioselectivity to occur. Generally, if the free ylide forms without any catalyst association then enantioselectivity is highly unlikely. 

Lipases from porcine pancreas (PPL) and from Aspergillus niger are uniquely suited for oxazolone hydrolysis since they catalyze the ring-opening reaction with a high degree of enantioselectivity. Moreover, these lipases exhibited opposite stereochemical preference, thus providing access to both enantiomers of A -benzoyl... 

Catalysts for ketone hydrogenation continue to be developed but one of the best systems is still the BINAP-DPEN catalyst first reported by Ohkuma et al. in 1995. " In this system ruthenium is combined with both a chiral diphosphine and a chiral diamine, forming an octahedral complex which gives a high degree of enantioselectivity. This stereoselectivity is considered to be a result of the synergistic effect of the chiral diphosphine and diamine ligands. 

To test the feasibility of enzyme-catalyzed enantiosective reactions in solid/gas reactors and to evaluate the efficiency of the resolution obtained in the gas phase compared to liquid systems, resolution of racemic 2-pentanol, catalyzed by CALB, through alcoholysis with methyl propanoate as acyl donor has been investigated in both liquid media and the gas phase [24]. As CALB has an enantiopreference for R enantiomers of secondary alcohols, this last reaction leads to S-2-Pentanol. This compound is a chiral intermediate in the synthesis of several potential anti-Alzheimer s drugs that inhibit 3-amyloid peptide release and/or its synthesis [25]. The degree of enantioselectivity was measured by using the enantiomeric ratio E, which is defined as the ratio of the specificity constants kcat/KM for the enantiomers (R/S in this case). E can be determined from the enantiomeric excess of... 

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