Enantiotopic selectivity

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(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... 

The breakthrough was achieved by D. A. Evans and coworkers " , who demonstrated that aryldimethylphosphine-borane complexes 195 are easily deprotonated by i-BuLi/(—)-sparteine (11), furnishing efficient enantiotopic selection between the methyl groups (equation 45). The intermediate lithium compound 196 was added to benzophenone (to give alcohols 197) or oxidatively coupled to furnish bisphosphines 198 with high ee. The major amount of the minor diastereomer epi-196 is removed as separable meso- 9. ... 

Enantiotopically selective ester hydrolysis can also be achieved enzymatically (Table 8). Eiflier one ester group in a me.ro-diester (103)-(1(M>) or one acetate in a me.m-diacetate (107) 111) are saponified with PLE or other lipases. In favorable cases enzymatic acylation and deacylation are stereochemically complementary and may thus be combined to gain access to bodi enantiomers, as illustrated by the example in Table 9. ... 

The reason why these enzymes have received considerable attention over the years is that they display a high degree of enantiotopic selectivity on the prochiral aldehyde and ketone substrates. The selectivity of these enzymes is in many instances masked by the rate of spontaneous racemization of the cyanohydrins, which are prone to racemization under non-acidic conditions. This balance of selectivity of the enzymes versus the competition with the spontaneous racemization reaction as a function of the pH was described as early as 1921 using the hydroxynitrile lyase enzyme from peach leaves [22], These early experiments describe one of the challenges of applying hydroxynitrile lyases on an industrial scale. 

AE of the meso-bisallylic alcohol 17 has also been examined [54]. In this class of substrate, the first epoxidation occurs smoothly in a highly enantiotopic selective manner to give the mono-epoxide 18 preferentially but the second epoxidation of 18 is slow. Therefore, the mono-epoxide 18 can be obtained as a major product in a highly enantiopure form (98% ee) together with a small amount of the diepoxide. 

Epoxidation of prochiral dialkenyl carbinols 28 provides the anti-epoxide 29 of extremely high optical purity [68, 69, 70]. The first epoxidation occurs in an enantiotopic selective manner while the second one proceeds in an enantiomer-differentiating manner (kinetic resolution). In the second step, the minor (R)-monoepoxides 30 are consumed faster than the major (S)-enantiomers 29 and therefore the enantiomeric excess of the major anfi-monoepoxide 29 increases as the reaction proceeds. If a reaction proceeds with a kfas(/ksio, =104, anti-syn selectivity for the fast reaction=98 2 and for the slow reaction=38 62, as observed in the epoxidation of racemic ( )-l-cyclohexyl-2-buten-l-ol,the enantiomeric excess of anti-29 on calculation is 99.4,99.96, and 99.994% ee at 50,99, and 99.9% conversion, respectively. Yields of anti-29 are 48,93 (maximum), and 91% at the respective conversions. Actually, in the epoxidation of 1,4-pentadien-... 

Kishimoto, D. and Kurihara, N. 1996. Effects of cytochrome P450 antibodies on the oxidative demethylation of methoxychlor catalyzed by rat liver microsomal cytochrome P450 isozymes isozyme specificity and alteration of enantiotopic selectivity. Pest. Biochem. Physiol., 56, 44—52. 

Kishimoto, D., Oku, A., and Kkurihara, N. 1995. Enantiotopic selectivity of cytochrome P450-catalyzed oxidative demethylation of methoxychlor alteration of selectivity depending on isozymes and substrate concentrations. Pest. Biochem. Physiol., 51,12-19. 

Groves examined the hydroxylation of optically active mono-deuterated ethylbenzene using optically active vaulted iron-porphyrin complex 2 as the catalyst and disclosed that d/ h was 6.4 and enantiotopic selectivity in the hydrogen atom abstraction step was 84% ee (A h/ sd = d/ h x [pro-.R]/ [pro-S] = 92 8). However, this enantiotopic selectivity is not directly reflected in the enantiomeric excess (77% ee) of the product (Scheme 3) [9]. These results indicate that hydrogen atom abstraction is the rate-determining step and that the reaction is not concerted but stepwise, and are well compatible with the oxygen rebound mechanism. Discrepancy between the enantiotopic selectivity and the enantiomeric excess is rationalized... 

Katsuki and coworkers examined enantiotopic selective hydroxylation of pro-chiral substrates with chiral (salen)manganese complexes as catalysts [13]. This reaction also proceeds via a radical intermediate [13a]. The kinetic isotopic effect (kn/kD = 4.6) observed in the hydroxylation of ethylbenzene with complex lib supports the idea that hydrogen atom abstraction is the rate-determining step [13b]. In the reaction using chiral (salen)manganese complexes which have no chiral cavity, radical decay should occur less selectively and should deteriorate the enan-tioselectivity of hydroxylation. A solvent of intense viscosity constitutes a strong... 

To directly reflect the enantiotopic selectivity in hydrogen atom abstraction in the ee of the resulting alcohol, the radical decay must be suppressed efficiently. To solve this problem, complex 11 in which the manganese ion is covered by the /-butyldiphenylsilyl group introduced into the phenyl substituent was synthesized [13b]. Good < es (84 and 83%) observed at the initial stage of the oxidation of 1,1-... 

Scheme 1 introduces the parameters that are used to describe the stereoselectivity of the monomer enchainment process. For chain-end control, the parameters Pm and refer to the probability of meso and racemic placements, respectively (the Bovey formalism is a convenient way to describe polymer tacticity, with a small m for meso, and a small r for racemic relationships between adjacent stereogenic centers). A Pm equal to unity indicates isotac-ticity, while a P equal to unity signifies syndiotac-ticity. For site-control mechanisms, the parameter a represents the degree of enantiotopic selectivity of the enchainment. When a is either 1 or 0 an isotactic polymer forms, while an a parameter of 0.5 produces an atactic polymer. Polymer architectures relevant to this review are shown in Figure 1. 

Chiral Catalysts Containing Group 7 Metals (Mn, Tc, and Re). Most of the chiral manganese complexes belong to the Mn(III)-salen-type complexes (Fig. 17), which are effective catalysts in asymmetric epoxidation (147). (The most widely used one is the Jacobsen s catalyst, iV,Ar -bis(3,5-di-terf-butylsalicylidene)-l,2-cyclohexanediamino-manganese(III) chloride.) These types of catalysts are also efficient for enantioselective aziridination (148), kinetic resolution of racemic allene via enantiomer differentiating oxidation (149), and enantiotopic selective... 

Enzymes - and thus hydrolases - can realize all kinds of selectivities such as chemo-, regio-, diastereomer and diastereotopic selectivity, as well as enantiomer and enantiotopic selectivity [83]. Accordingly, lipases were apphed in all possible kinds of stereoselective biotransformations [29, 30, 79, 81, 83] such as KR [79, 84], deracemization, and dynamic kinetic resolution (DKR) [85]. In this review, we wish to concentrate on methods enabling the continuous-mode hydrolase-mediated production of compounds in high enantiomeric purity. 

Although with lipase-catalyzed acylations all types of selectivities including enantiotopic selectivity can be realized [29, 30, 60, 79, 81, 83], there are only a few examples of hydrolase-catalyzed enantioselective biotransformations in real flow-through mode (Figure 9.6). 

Figure 5. Enantiotopic selectivity in the oxidative mono-demethylation of methoxychlor by precision-cut rat, mouse, Japanese quad and rainbow trout liver slices. The amounts of corresponding conjugates are also included in this...

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