This is an overview of successes in the realm of catalytic homogeneous asymmetric hydrogenation of substrates primarily of interest in the synthesis of pharmaceuticals in order to identify important problems still unsolved. First, tables are provided that list the successful reductions to over 90% enantiomeric excess of prochiral ketones to alcohols, imines to amines, and olefins to saturated carbon centers. Noted in the tables are the metal (including "green" metals Mn, Fe, and Co) or enzyme, the class of ligand, the conditions of the medium, and the scale of reduction, if over 1 kg of product, as well as the nature of the process, whether direct hydrogenation using H 2 gas (DH), transfer hydrogenation (TH), or hydrogenation with dynamic kinetic resolution (DKR). Tables of representative pharmaceutical or fine chemicals products are provided for each class of substrate. With this overview, the opportunities for further research and development become clearer.

A slight change in the iron catalyst structure (amine arm with PEt2 to imine arm with PPh2) results in a complete reversal of the enantioselectivity toward ketone reduction.

The use of manganese in homogeneous hydrogenation catalysis has been a recent focus in the pursuit of more environmentally benign base metal catalysts. It has great promise with its unique...

Two borane-functionalized bidentate phosphine ligands that vary in tether length have been prepared to examine cooperative metal−substrate interactions. Ni(0) complexes react with aryl azides at low temperatures to form structurally unusual κ 2 -(N,N)-N 3 Ar adducts. Warming these adducts affords products of N 2 extrusion and in one case, a Ni-imido compound that is capped by the appended borane. Reactions with 1-azidoadamantane (AdN 3 ) provide a distinct outcome, where a proposed nickel imido intermediate activates the sp 2 C−H bonds of arenes, even in the presence of benzylic C−H sites. Combined experimental and computational mechanistic studies demonstrate that the unique reactivity is a consequence of Lewis-acid-induced polarization of the Ni−NR bond, potentially providing a synthetic strategy for chemoselective reaction engineering.