Abstract
The enantioselective amination of C(sp3)–H bonds is a powerful synthetic transformation yet highly challenging to achieve in an intermolecular sense. We have developed a family of anionic variants of the best-in-class catalyst for Rh-catalyzed C–H amination, Rh2(esp)2, with which we have associated chiral cations derived from quaternized cinchona alkaloids. These ion-paired catalysts enable high levels of enantioselectivity to be achieved in the benzylic C–H amination of substrates bearing pendant hydroxyl groups. Additionally, the quinoline of the chiral cation appears to engage in axial ligation to the rhodium complex, providing improved yields of product versus Rh2(esp)2 and highlighting the dual role that the cation is playing. These results underline the potential of using chiral cations to control enantioselectivity in challenging transition-metal-catalyzed transformations.
Highlights
The enantioselective amination of C(sp3)−H bonds is a powerful synthetic transformation yet highly challenging to achieve in an intermolecular sense
The original catalysts used for this purpose were dirhodium tetracarboxylates,[3] and extensive development of this methodology has been undertaken by Du Bois and co-workers in particular.2a This has culminated in the development of the versatile and robust strapped dicarboxylate catalyst Rh2(esp)[2] which can perform rhodiumcatalyzed C−H amination intermolecularly on benzylic, tertiary, and, in some cases, secondary alkyl C−H bonds (Figure 1a).2a,4 In many instances, C−H amination leads to the introduction of a new stereocenter and efforts to render Rh(II)-catalyzed C−H aminations enantioselective have been ongoing since its early development.[5]
The ligand is made anionic through the attachment of a sulfonate group which in turn allows association of a chiral cation with which to exert enantiocontrol (Figure 1c).[16]
Summary
The enantioselective amination of C(sp3)−H bonds is a powerful synthetic transformation yet highly challenging to achieve in an intermolecular sense. These anionic handles would be used to associate with chiral cations to form a “sulfonesp” family of ion-paired catalysts (Figure 1d).
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