page_title: Asymmetric hydrogenation
section_title: Imines and ketones
hierarchical_section_title: Asymmetric hydrogenation / Acyclic substrates / Imines and ketones
caption_attribution_description: English: An archetypal structure for Noyori's asymmetric ketone hydrogenation catalyst
context_page_description: Asymmetric hydrogenation is a chemical reaction that adds two atoms of hydrogen preferentially to one of two faces of an unsaturated substrate molecule, such as an alkene or ketone. The selectivity derives from the manner that the substrate binds to the chiral catalysts. In jargon, this binding transmits spatial information from the catalyst to the target, favoring the product as a single enantiomer. This enzyme-like selectivity is particularly applied to bioactive products such as pharmaceutical agents and agrochemicals.
  A generic asymmetric hydrogenation of N-acetyl dehydroaminoacids
context_section_description: Ketones and imines are related functional groups, and effective technologies for the asymmetric hydrogenation of each are also closely related. Of these, Noyori's ruthenium-chiral diphosphine-diamine system is perhaps one of the best known. It can be employed in conjunction with a wide range of phosphines and amines (where the amine may be, but need not be, chiral) and can be easily adjusted for an optimal match with the target substrate, generally achieving enantiomeric excesses (ee's) above 90%.
  For carbonyl and imine substrates, end-on, η¹ coordination can compete with η² mode. For η¹-bound substrates, the hydrogen-accepting carbon is removed from the catalyst and resists hydrogenation.
  Iridium/P,N ligand-based systems are also commonly used for the asymmetric hydrogenation of ketones and imines.  For example, a consistent system for benzylic aryl imines uses the P,N ligand SIPHOX in conjunction with iridium(I) in a cationic complex to achieve asymmetric hydrogenation with ee >90%. One of the most efficient and effective catalysts ever developed for the asymmetric hydrogenation of ketones, with a turnover number (TON) up to 4,550,000 and ee up to 99.9%, uses another iridium(I) system with a closely related tridentate ligand.
  Highly effective system for the asymmetric hydrogenation of ketones
  Despite their similarities, the two functional groups are not identical; there are many areas where they diverge significantly.  One of these is in the asymmetric hydrogenation of N-unfunctionalized imines to give primary amines. Such species can be difficult to selectively reduce because they tend to exist in complex equilibria of imine and enamine tautomers, as well as (E) and (Z) isomers.  One approach to this problem has been to use ketimines as their hydrochloride salt and rely on the steric properties of the adjacent alkyl or aryl groups to allow the catalyst to differentiate between the two enantiotopic faces of the ketimine.
caption: Noyori catalyst for asymmetric hydrogenation of ketones.
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