Application of Chiral Mixed Phosphorus/Sulfur Ligands to Enantioselective Rhodium-Catalyzed Dehydroamino Acid Hydrogenation and Ketone Hydrosilylation Processes

Abstract

Chiral mixed phosphorus/sulfur ligands 1-3 have been shown to be effective in enantioselective Rh-catalyzed dehydroamino acid hydrogenation and ketone hydrosilylation reactions (eqs 1, 2). After assaying the influence of the substituents at sulfur, the substituents on the ligand backbone, the relative stereochemistry within the ligand backbone, and the substituents at phosphorus, ligands 2c (R = 3,5-dimethylphenyl) and 3 were found to be optimal in the Rh-catalyzed hydrogenation of a variety of alpha-acylaminoacrylates in high enantioselectivity (89-97% ee). A similar optimization of the catalyst for the Rh-catalyzed hydrosilylation of ketones showed that ligand 3 afforded the highest enantioselectivities for a wide variety of aryl alkyl and dialkyl ketones (up to 99% ee). A model for asymmetric induction in the hydrogenation reaction is discussed in the context of existing models, based on the absolute stereochemistry of the products and the X-ray crystal structures of catalyst precursors and intermediates.

Palladium(II)‐katalysierte C‐H‐Aktivierung/C‐C‐Kreuzkupplung: Vielseitigkeit und Anwendbarkeit

“…Bemerkenswerterweise ist dieses Konzept eng mit der grundlegenden Arbeit von Evans und Mitarbeitern verwandt, die das rationale Design eines chiralen gemischten Phosphor/Schwefel-Liganden für die asymmetrische Hydrierung beschreiben, bei dem der chirale Schwefel ebenfalls durch einen "Zahnradeffekt" angeordnet ist. [97] Um die Anwendbarkeit dieser Reaktion zu erweitern, untersuchten wir die Kupplung von prochiralen C(sp 3 )-HBindungen. Die Liganden der Tabelle 4 ergaben nur geringe Enantioselektivitäten (10-15 % ee).…”

Convenient Enantioselective Hydrosilylation of Ketones Catalyzed by Zinc‐Macrocyclic Oligoamine Complexes

“…[12] High enantioselectivities (over 90% ee) for the standard AHS of acetophenone were achieved with chiral diphosphine [13] or pyridine-phosphine [14] ligands having a ferrocene structural unit, as well as with a chiral P,S ligand reported by Evans. [15] Recently chiral CA C H T U N G T R E N N U N G (carbene),N ligands for rhodium [16] and N-heterocyclic carbene ligands for ruthenium [17] were introduced. However, the catalytic systems based on rhodium or ruthenium generally suffer from their high cost and require elaborate preparation.…”

Ligand Design for Catalytic Asymmetric Reduction

“…A Rh complex with a C 1 -chiral P/S mixed ligand, (R,R)-L1 (see Figure 1.2), catalyzes hydrogenation of methyl (Z)-2-(acetamido)cinnamate to afford the S product in excellent ee. 28 The enamide substrate is reduced along with the catalytic cycle illustrated in Figure 1.3. However, unlike traditional catalyst systems, the stereochemistry of hydrogenation product suggests that the major S product is obtained via the most stable diastereomer of 3B.…”

“…The high enantiodiscriminatory ability of the catalyst is rationalized by means of the quadrant model of Re-3B-L1. 28 The electron-donating olefin function of the enamide substrate preferably binds to Rh at the trans position to the less electron-donating sulfur atom instead of phosphorus, that is, the first and fourth quadrants are unfavorable for the olefinic function for electronic reasons. The third and fourth quadrants are blocked by equatorial P-phenyl and bulky S-t-butyl group, respectively.…”