Enantioselectivity hydride donor addition

Significantly better results in addition of non-stabilized nucleophiles have come from hydrogenolysis reactions using formate as a hydride donor as shown in Scheme 8E.46. The racemic cyclic acetate and prochiral linear carbonates were reduced in good enantioselectivities by monophosphine ligands (/ )-MOP (16) and (Zf)-MOP-phen (17), respectively [195]. The chirality of the allylsilane can be efficiently transferred to the carbinol center of the homoallylic alcohol by the subsequent Lewis acid catalyzed carbonyl addition reaction 1196], The analogous... 

Enantioselective Addition of Hydride Donors to Carbonyl Compounds... 

The hydride donor of the Noyori reduction of ketones is the hydrido aluminate K-BINAE-H shown in Figure 10.23 or its enantiomer S-BINAL-H. The new C—H hond is presumably formed via a cyclic six-memhered transition state of stereostructure A. Unfortunately, there is no easy way to rationalize why enantioselectivity in this kind of addition is limited to substrates in which the carbonyl group is flanked by one conjugated substituent (C=C, aryl, C=C). The suggestion that has been made is that a lone pair on the axial oxygen of the BINOL unit in the transition state undergoes a repulsive interaction with pi electrons in the unsaturated ketone if the latter is also axial. 

Additional investigations by Keay and coworkers [57] provide insight into the effects of various solvents and bases on Pd-BE JAP-catalysed polycyclizations to form tetracyclic products 95a and 95e. These studies showed that the use of dioxane as solvent or PMP as base promotes formation of the undesired tricyclic product, because both reagents can serve as hydride donors. Further experiments showed that l,4-diazabicyclo[2.2.2]octane (DABCO), which is an ineffective hydride donor because of its bridged structure, can be substituted for PMP to reduce formation of by-product 96 without significant loss of enantioselectivity. Likewise, the use of toluene rather than dioxane as the solvent maximizes conversion to the desired tetrayclic products. 

Catalytic asymmetric Michael addition is an important reaction for creating carbon-carbon bonds with enantioselectivity. This reaction can be combined with other catalytic transformations to build up complex organic structures. A successful example is the enantioselective cascade Michael addition/H -hydrogenation catalyzed by ruthenium hydride borohydride complexes containing P-aminophosphine ligands 26 (Scheme 5.13) [19]. This approach has been extended to pentenones, heptenones, and nitrostyrene Michael acceptors and malonitrile Michael donors. 

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