Stereogenic enantiopure substrate

In the hydrogenation of diketones by Ru-binap-type catalysts, the degree of anti-selectivity is different between a-diketones and / -diketones [Eqs (13) and (14)]. A variety of /1-diketones are reduced by Ru-atropisomeric diphosphine catalysts to indicate admirable anti-selectivity, and the enantiopurity of the obtained anti-diol is almost 100% (Table 21.17) [105, 106, 110-112]. In this two-step consecutive hydrogenation of diketones, the overall stereochemical outcome is determined by both the efficiency of the chirality transfer by the catalyst (catalyst-control) and the structure of the initially formed hydroxyketones having a stereogenic center (substrate-control). The hydrogenation of monohydrogenated product ((R)-hydroxy ketone) with the antipode catalyst ((S)-binap catalyst) (mis-... 

Krische and coworkers [44] developed a Rh-catalyzed asymmetric domino Michael/aldol reaction for the synthesis of substituted cyclopentanols and cyclohex-anols. In this process, three contiguous stereogenic centers, including a quaternary center, are formed with excellent diastereo- and enantioselectivity. Thus, using an enantiopure Rh-BINAP catalyst system and phenyl boronic acid, substrates 2-108 are converted into the correspondding cyclized products 2-109 in 69-88% yield and with 94 and 95% ee, respectively (Scheme 2.24). 

Nonactivated tertiary hydrocarbon sites of enantiopure compounds 210 are oxyfunctionalized enantiospecifically by perfluoro-a.r-2- -butyl-3- -propyloxaziridine 80 under remarkably mild reaction conditions (Equation 8) <19990L281>. The reaction occurs with retention of the configuration at the oxidized stereogenic center and the enantiospecificity is highly independent of both the carbon framework of the substrate as well as functional groups (Table 16). 

The linear synthesis of the title compound started from an enantiopure building block with one stereogenic center. The other six stereogenic centers were introduced by two reagent-controlled Evans aldol reactions, an unselective 1,3-dipolar cycloaddition with subsequent separation of the diastereomers, and a substrate-controlled epoxidation step. 

ADHs were screened for this purpose and ADH-A from Rhodoccocus ruber could furnish the (S)-enantiomer with perfect enantiopurity (>99% ee) and 93% isolated yield. Reducing equivalents were provided by isopropanol in a coupled-substrate approach and allowed the use of catalytic amounts of NADH. The product from the enzymatic reduction required stereoinversion of the stereogenic center en route to the more active (R)-form of ramatroban. This was performed by converting the alcohol into the amine via the azide form, in a combined Mitsunobu-Staudinger one-pot reaction at low temperature [27]. 

The first step for a successfid memory of chirality reaction should involve deprotonation of the stereogenic center in the enantiopure reactant (S)-substrate forming a conformationally chiral reactive (Af)-intermediate with high enantioselectivity. The helical descriptors (A/)- and Py are used to describe the chirality of the intermediates (see section 1.3.8). Most importantly, the conformationally chiral (M)-intermediate should not racemize easily on the time scale of the desired subsequent reaction. The final criterion is that the conformationally chiral intermediate must... 

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