Achiral Ligands Dramatically Enhance Rate and Enantioselectivity in the Rh/Phosphoramidite‐Catalyzed Hydrogenation of α,β‐Disubstituted Unsaturated Acids

Abstract

In 2000, three research groups demonstrated that the widely held view that chiral bidentate ligands are necessary to achieve high enantioselectivity in rhodium-catalyzed hydrogenations needs revision. Monodentate phosphonites, [1a] phosphites [1b] and phosphoramidites [1c] proved to be highly versatile ligands for this important transformation and afforded excellent enantioselectivities for a broad range of substrates.

Better Performance of Monodentate P‐Stereogenic Phosphanes Compared to Bidentate Analogues in Pd‐Catalyzed Asymmetric Allylic Alkylations

“…Heterocombinations of monodentate chiral phosphonites with achiral phosphites or phosphanes [33] and chiral phosphoramidites with achiral phosphanes [34] improved the conversion and enantioselectivity in the Rh-catalyzed hydrogenation reactions compared to the systems formed by homocombination of two chiral ligands. This strategy has been further extended.…”

Industrial Catalysts for Regio‐ or Stereo‐Selective Oxidations and Reductions. A Review of Key Technologies and Targets

“…It is estimated that large volumes of this intermediate will be required in the future but the best ee reported so far for production of this intermediate is 95 % as shown in Figure 1.8. [9] A study by Hoen et al [10] in collaboration with scientists from DSM indicates that the MONOPHOS derivative (D) together with added triphenylphosphine improves both the rate of reaction and enantioselectivity and may offer an improved system for this important target as can be seen from the analogous reaction reported by these authors and shown in Figure 1.9. The drug candidate OPC-51803 is the first nonpeptide vasopressin V 2 -receptorselective agonist that is in phase II clinical trials and the best chiral reduction to the intermediate acid (E) was with ruthenium acetate-[(S)-H8-BINAP] that gave a 77 % ee [11] (Figure 1.10).…”

Supported Chiral Monodentate Ligands in Rhodium‐Catalysed Asymmetric Hydrogenation and Palladium‐Catalysed Asymmetric Allylic Alkylation

“…[29] NMR studies have revealed that homocombinations, e.g., (P a ) 2 M; see Equation (1), are present in the mixture and these species can lower the overall catalytic performance of the system. [30] P a + P b + M Ǟ (P a ) 2 M + P a P b M + (P b ) 2 M…”