Coordination determined chemo- and enantioselectivities in asymmetric hydrogenation of multi-functionalized ketones

Chiral secondary alcohols are ubiquitous motifs in numerous natural products, pharmaceuticals, and biological active compounds. Catalytic asymmetric hydrogenation of multi-functionalized ketones provides an effective and powerful synthesis method to construct chiral secondary alcohols. In the asymmetric hydrogenation of multi-functionalized ketones, the simultaneous coordination of the carbonyl oxygen of ketones and adjacent functional groups to central metal of the catalyst is the key factor for the asymmetric induction. However, for ketones with two adjacent coordinating groups, the competitive ligation of the adjacent coordinating groups to central metal tends to decrease the enantioselectivities. In this review, we summarized the know how in achieving high chemo-, enantio-, and diastereoselectivities in asymmetric hydrogenation of multi-functionalized ketones, i.e. to change the bulkiness and/or electronic properties of the coordinating groups in substrates and in ligands, or to introduce a third coordinating ligand (solvent) to make one coordination much more stronger than the other.