Key words
asymmetric reduction - ketones - transfer hydrogenation - hydrogenation - hydrosilylation - iron catalysis
The development of catalytic methods for the asymmetric reduction of keto groups, particularly in 2-pyridine ketones, has garnered considerable interest due to the transformative potential of these reactions in the synthesis of enantiomerically pure compounds. Enantiopure chiral 2-pyridine aryl/alkyl alcohols are not only essential intermediates in creating chiral ligands, such as Bolm’s ligand, but are also foundational in the synthesis of complex, stereochemically defined molecules in fields like pharmaceuticals and materials science. As a result, there has been substantial effort to design catalysts that facilitate these reductions with high enantioselectivity, efficiency, and versatility.
A wide array of catalytic approaches has emerged for the asymmetric reduction of 2-pyridine ketones, utilizing transition metals such as iron, manganese, ruthenium, copper, rhodium, and iridium. These systems often differ significantly in their mechanistic pathways, with some involving direct hydrogenation, others employing transfer hydrogenation, and others relying on hydrosilylation. Each method offers unique advantages, yet also presents challenges related to reaction scope, operational simplicity, cost, scalability, and environmental impact, with green chemistry principles driving much of the recent innovation in this field.
Despite these advancements, there remain open questions and unsolved challenges, particularly in the quest for more sustainable, non-precious metal catalysts and methods that maximize atom economy. Furthermore, the sheer pace of development in this area can sometimes obscure which transformations have reached maturity and which require further optimization or exploration. This graphical review seeks to clarify these developments, providing a structured overview of current catalytic systems for asymmetric reduction of 2-pyridine ketones. By highlighting well-established techniques alongside emerging approaches, it aims to illuminate future directions for research, particularly in the context of eco-friendly synthetic methodologies and the expanding role of iron-based catalysis in asymmetric synthesis.
Figure 1 Catalytic asymmetric transfer hydrogenation using iridium and iron[1]
Figure 2 Catalytic asymmetric transfer hydrogenation using iron and rhodium[2]
Figure 3 Catalytic asymmetric transfer hydrogenation using rhodium and ruthenium[3]
Figure 4 Ruthenium-catalyzed asymmetric transfer hydrogenation[4]
Figure 5 Ruthenium-catalyzed asymmetric transfer hydrogenation (cont.)[5]
Figure 6 Iridium-catalyzed asymmetric hydrogenation[6]
Figure 7 Catalytic asymmetric hydrogenation using iridium, iron and manganese[7]
Figure 8 Catalytic asymmetric hydrogenation using manganese, rhodium and ruthenium[8]
Figure 9 Catalytic asymmetric hydrogenation using ruthenium and other reactions[9]
Figure 10 Copper-catalyzed asymmetric hydrosilylation[10]
Figure 11 Catalytic asymmetric hydrosilylation using copper, iron and rhodium[10h]
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