6.4 KiB
| title | chunk | source | category | tags | date_saved | instance |
|---|---|---|---|---|---|---|
| Asymmetric hydrogenation | 2/4 | https://en.wikipedia.org/wiki/Asymmetric_hydrogenation | reference | science, encyclopedia | 2026-05-05T10:46:00.770091+00:00 | kb-cron |
hydrides, which transfer to the unsaturated substrate diamines, which interact with substrate and with base activator by the second coordination sphere diphosphine, which confers asymmetry. The "Noyori-class" of catalysts are often referred to as bifunctional catalysts to emphasize the fact that both the metal and the (amine) ligand are functional. In the hydrogenation of C=O containing substrates, the mechanism was long assumed to operate by a six membered pericyclic transition state/intermediate whereby the hydrido ruthenium hydride center (HRu-NH) interacts with the carbonyl substrate R2C=O. More recent DFT and experimental studies have shown that this model is largely incorrect. Instead, the amine backbone interacts strongly with the base activator, which often is used in large excess. However in both cases, the substrate does not bond directly with the metal centre, thus making it a great example of an outer sphere mechanism.
== Metals == Practical AH employ platinum metal-based catalysts.
=== Base metals === Iron is a popular research target for many catalytic processes, owing largely to its low cost and low toxicity relative to other transition metals. Asymmetric hydrogenation methods using iron have been realized, although in terms of rates and selectivity, they are inferior to catalysts based on precious metals. In some cases, structurally ill-defined nanoparticles have proven to be the active species in situ and the modest selectivity observed may result from their uncontrolled geometries.
== Ligand classes ==
=== Phosphine ligands === Chiral phosphine ligands, especially C2-symmetric ligands, are the source of chirality in most asymmetric hydrogenation catalysts. Of these the BINAP ligand is well-known, as a result of its Nobel Prize-winning application in the Noyori asymmetric hydrogenation. Chiral phosphine ligands can be generally classified as mono- or bidentate. They can be further classified according to the location of the stereogenic centre – phosphorus vs the organic substituents. Ligands with a C2 symmetry element have been particularly popular, in part because the presence of such an element reduces the possible binding conformations of a substrate to a metal-ligand complex dramatically (often resulting in exceptional enantioselectivity).
==== Monodentate phosphines ==== Monophosphine-type ligands were among the first to appear in asymmetric hydrogenation, e.g., the ligand CAMP. Continued research into these types of ligands has explored both P-alkyl and P-heteroatom bonded ligands, with P-heteroatom ligands like the phosphites and phosphoramidites generally achieving more impressive results. Structural classes of ligands that have been successful include those based on the binapthyl structure of MonoPHOS or the spiro ring system of SiPHOS. Notably, these monodentate ligands can be used in combination with each other to achieve a synergistic improvement in enantioselectivity; something that is not possible with the diphosphine ligands.
==== Chiral diphosphine ligands ==== The diphosphine ligands have received considerably more attention than the monophosphines and, perhaps as a consequence, have a much longer list of achievement. This class includes the first ligand to achieve high selectivity (DIOP), the first ligand to be used in industrial asymmetric synthesis (DIPAMP) and what is likely the best known chiral ligand (BINAP). Chiral diphosphine ligands are now ubiquitous in asymmetric hydrogenation.
==== P,N and P,O ligands ====
The use of P,N ligands in asymmetric hydrogenation can be traced to the C2 symmetric bisoxazoline ligand. However, these symmetric ligands were soon superseded by monooxazoline ligands whose lack of C2 symmetry has in no way limits their efficacy in asymmetric catalysis. Such ligands generally consist of an achiral nitrogen-containing heterocycle that is functionalized with a pendant phosphorus-containing arm, although both the exact nature of the heterocycle and the chemical environment phosphorus center has varied widely. No single structure has emerged as consistently effective with a broad range of substrates, although certain privileged structures (like the phosphine-oxazoline or PHOX architecture) have been established. Moreover, within a narrowly defined substrate class the performance of metallic complexes with chiral P,N ligands can closely approach perfect conversion and selectivity in systems otherwise very difficult to target. Certain complexes derived from chelating P-O ligands have shown promising results in the hydrogenation of α,β-unsaturated ketones and esters.
==== NHC ligands ====
Simple N-heterocyclic carbene (NHC)-based ligands have proven impractical for asymmetrical hydrogenation. Some C,N ligands combine an NHC with a chiral oxazoline to give a chelating ligand. NHC-based ligands of the first type have been generated as large libraries from the reaction of smaller libraries of individual NHCs and oxazolines. NHC-based catalysts featuring a bulky seven-membered metallocycle on iridium have been applied to the catalytic hydrogenation of unfunctionalized olefins and vinyl ether alcohols with conversions and ee's in the high 80s or 90s. The same system has been applied to the synthesis of a number of aldol, vicinal dimethyl and deoxypolyketide motifs, and to the deoxypolyketides themselves. C2-symmetric NHCs have shown themselves to be highly useful ligands for the asymmetric hydrogenation.
== Acyclic substrates == Substrates can be classified according to their polarity. Nonpolar substrates are dominated by alkenes. Polar substrates include ketones, enamines ketimines.
=== Nonpolar substrates ===
Alkenes that are particularly amenable to asymmetric hydrogenation often feature a polar functional group adjacent to the site to be hydrogenated. In the absence of this functional group, catalysis often results in low ee's. For some unfunctionalized olefins, iridium with P,N-based ligands) have proven effective, however. Alkene substrates are often classified according to their substituents, e.g., 1,1-disubstituted, 1,2-diaryl trisubstituted, 1,1,2-trialkyl and tetrasubstituted olefins. and even within these classes variations may exist that make different solutions optimal.