Kinetic enantioselectivity

The ready availability of the transketolase (TK E.C. 2.2.1.1) from E. coli within the research collaboration in G. A. Sprenger s group suggested the joint development of an improved synthesis of D-xylulose 5-phosphate 19, which was expensive but required routinely for activity measurements [27]. In vivo, transketolase catalyzes the stereospecific transfer of a hydroxyacetyl nucleophile between various sugar phosphates in the presence of a thiamine diphosphate cofactor and divalent cations, and the C2 donor component 19 offers superior kinetic constants. For synthetic purposes, the enzyme is generally attractive for its high asymmetric induction at the newly formed chiral center and high kinetic enantioselectivity for 2-hydroxyaldehydes, as well as its broad substrate tolerance for aldehyde acceptors [28]. 

At the end of 2007, Widenhoefer et al. reported the first examples of the dynamic kinetic enantioselective hydroamination of axially chiral allenes, catalyzed by a dinuclear complex of gold (Figure 8.1) and silver perchlorate [46, 47]. 

The rabbit FruA discriminates the enantiomers of its natural substrate with a 20 1 preference for D-GA3P (12) over its L-antipode [202], Assistance from anionic binding was revealed by a study on a homologous series of carboxylated 2-hydroxyaldehydes which showed optimum enantioselectivity when the distance of the charged group equaled that of 12 (Scheme 15, Fig. 11) [299], The resolution of racemic substrates is not, however, generally useful since the kinetic enantioselectivity for nonionic aldehydes is rather low [202], 3-Azido substituents (69) can lead to an up to 9-fold preference of enantiomers in kinetically controlled experiments [300] while hydroxyl (70 preference for the... 

The first strategy involves discrimination between enantiotopic leaving groups (Type A). In the second approach, two enantiomers of a racemic substrate converge into a meso-n-al y complex wherein preferential attack of the nucleophile at one of either allylic termini leads to asymmetric induction, a process that may be referred to as a dynamic kinetic enantioselective transformation (Type B). The third requires differentiation between two enantiotopic transition... 

The enantioselective hydroaminations of allenes with chiral phosphine catalysts was accomplished with substrates that had a terminal symmetric substitution and with the amines protected as carbamates or sulfonamides. The same symmetric substituents were necessary for the enantioselective transformation nsing chiral counterions. However, very recently, high enantiomeric excesses were reached with trisubstituted asymmetric allenes by a dynamic kinetic enantioselective hydroamination of allenyl carbamates (eqnation 110), even thongh the E/Z ratio of the prodncts was not optimal. 

Paquette s group has recently synthesized and evaluated chiral 4-sub-stituted triazolinediones in Diels-Alder cycloadditions.63 For example, endo-(-)-bomylamine has been converted to an azo dienophile, which has been used to resolve 1,2,3-trimethylcyclooctatetraene (Scheme 6-VII). In addition, triazolinediones derived from a-methylbenzylamine and dehydroabietylamine have been prepared and their reactions with achiral 1,3-dienes were investigated.636 Unfortunately, these dienophiles did not show good kinetic enantioselection, but they are useful for the type of resolution shown in Scheme 6-VII.630... 

Chan VS, Bergman RG, Toste FD (2007) Pd-catalyzed dynamic kinetic enantioselective arylation of silylphosphines. J Am Chem Soc 129 15122-15123... 

Affinity of anions to the neutral zwitterionic form 9 is expectedly much lower, and for TV-Ac-Phe, which still shows a noticeable affinity, the enantioselectivity is inverted (Table 7). The zwitterion is an efficient catalyst for the hydrolysis of p-nitrophenyl carboxylates, which involves the nucleophilic attack of the deprotonated phenol hydroxyls on the ester group of the substrate, with a small kinetic enantioselectivity in the cleavage of esters of TV-protected phenylalanine. 

On the other hand, the asymmetric reduction using formic acid proceeds irreversibly with kinetic enantioselection and, in principle, 100% conversion. However, this bifunctional Ru catalyst also efficiently promotes hydrogenation of CO2 to give formic acid and its derivatives [28]. Therefore, effective removal of CO2 with inert gas allow complete conversion, in particular, in a large-scale reaction. 

Zhang Z, Bender CF, Widenhoefer RA. Gold(I)-catalyzed dynamic kinetic enantioselective intramolecular hydroamination of allenes. J. Am. Chem. Soc. 2007 129(46) 14148-14149. 

Real-time ultrafast 2D NMR observations of an acetal hydrolysis at natural abundance have enabled observation of the reactive hemiacetal intermediate. Mutual kinetic enantioselection (MKE) and enantioselective kinetic resolution (KR) have been explored for aldol coupling reactions of ketal- and dithioketal-protected -ketoaldehydes expected to have high Felkin diastereoface selectivity with a chiral ketone enolate. ... 

The Zn -dependent aldolases facilitate an effective kinetic resolution of racemic 2-hydroxy aldehydes (rac-34) as substrates by an overwhelming preference (d.e. 95) for the L-configurated enantiomers l-34 which allows one to control three contiguous centers (e.g., 35/36 Fig. 17) of chirality in the products [110,111]. The kinetic enantioselectivity of class I aldolases, however, with nonanionic aldehydes is rather low [93,112]. 

Figure 17 Racemate resolution by class II DHAP aldolases due to their kinetic enantioselectivity for L-configurated a-hydroxyaldehyde substrates [110,111].

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