Enantioselective reduction metal catalyzed oxidation

Pu and co-workers incorporated atropisomeric binaphthols in polymer matrixes constituted of binaphthyl units, the macromolecular chiral ligands obtained being successfully used in numerous enantioselective metal-catalyzed reactions,97-99 such as asymmetric addition of dialkylzinc reagents to aldehydes.99 Recently, they also synthesized a stereoregular polymeric BINAP ligand by a Suzuki coupling of the (R)-BINAP oxide, followed by a reduction with trichlorosilane (Figure 10).100... 

P-chiral phosphines, which are potential ligands for transition metal-catalyzed reactions, were synthesized through hpase-catalyzed optical resolution of the corresponding racemic phosphine oxide compounds (Fig. 10.29). For example, lipase from C. rugosa (CRL) was used for the enantioselective hydrolysis of acetoxynaphthyl phosphine oxide (Fig. 10.29(a)). The P-enantiomer was hydrolyzed selectively, leaving the (S)-acetoxy compound, which was further subjected to chemical hydrolysis. Both enantiomeric phosphine oxides were obtained in >95% after recrystallization. Methylation followed by reduction with triethyl amine/trichlorosilane, with inversion of configuration, yielded the desired chiral phosphine. 

At this stage, sulfoximines had been shown to function as chiral ligands for various palladium and copper catalysts which led to enantioselectivities of >95% ee in various reactions. Furthermore, most of those catalyzed reactions were C-C bond formations. Obvious questions were, therefore, whether sulfoximines could also be applied in combination with other metals and whether reductions and oxidations could be catalyzed as well. A structural comparison of the sulfoximines leading to high ee values such as 55, 60, 81, and 85 revealed that all of them had a two-carbon distance between the two coordinating atoms (which were all nitrogen in these cases). 

On the contrary, to achieve a successful cinchona-catalyzed asymmetric oxidation chemistry, cinchona-catalyzed asymmetric reduction has been explored very little despite the importance of this reaction. Previous reports on this subject are restricted to the reduction of aromatic ketones and, moreover, the enantioselectivities achieved to date remain far from satisfactory when compared with metal catalysis. 

In contrast to asymmetric oxidation chemistry, cinchona-catalyzed asymmetric reduction reactions have been explored very little, despite the importance of this reaction. Previous reports on this topic are restricted to the reduction of aromatic ketones, and the enantioselectivities achieved to date remain far from satisfactory when compared with metal catalysis. Moreover, Hantsch esters, another type of useful organic hydrides, have not yet been studied in combination with cinchona catalysts. However, as is well known, the structures of cinchona alkaloids are easily modifiable, thus permitting the easy tuning of the reaction course. The successful use of cinchona catalysts for this reaction will therefore likely be reported in the very near future. 

Recently the first use of the paracyclophane backbone for the placement of two diphenylphosphano groups to give a planar chiral C2-symmetric bisphos-phane was reported [102]. The compound 159 abbreviated as [2.2]PHANEPHOS was used as a ligand in Rh-catalyzed hydrogenations. The catalytic system is exceptionally active and works highly enantioselective [ 103]. The preparation of [2.2]PHANEPHOS starts with rac-4,12-dibromo[2.2]paracyclophane (rac-157), which was metalated, transmetalated and reacted with diphenylphosphoryl chloride to give racemic bisphosphane oxide (rac-158). Resolution with diben-zoyltartaric acid and subsequent reduction of the phosphine oxides led to the enantiomerically pure ligand 159. 

Iridium has been found to be a very robust late transition metal which can mediate or catalyze C—H bond activation reactions very efficiently. However, the highly enantioselective Ir-catalyzed C—H bond functionalization via a transient C—Ir species for the construction of C—C or C—X bonds only emerged recently. Mechanistically, the catalytic cycle starts with oxidative addition of the Ii catalyst to the inert C—H bonds (such as aromatic, olefinic, or aliphatic C—H bonds), which are usually assisted with an ortho directing group. Subsequently, the formed C—Ir species inserts into an unsaturated functionality such as alkene, alkyne, or imine, delivering a new C—Ir speeies. Finally, the reductive elimination releases the products and regenerates the Ir catalyst. 

Homogeneous catalysts play an important role in industry as well as in research laboratories. Established applications include, for example, polymerization processes with zirconocene and its derivatives, rhodium- or cobalt-catalyzed hydroformylation of olefins, and enantioselective isomerization catalysts for the preparation of menthol. In contrast to heterogeneous catalysts, more experimental studies of reaction mechanisms are available and the active species can be characterized experimentally in some cases. Most catalysts are based on transition metal compounds, for which electronic structures and properties are well studied theoretically. A substantial number of elementary reactions, such as reductive elimination, oxidative addition, alkene or carbonyl migratory insertion, etc., have been experimentally Studied in detail by means of isotopic, NMR, and IR studie.s, as well as theoretically. ... 

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