Enantioselective and Diastereoselective Ir-Catalyzed Hydrogenation of α-Substituted β-Ketoesters via Dynamic Kinetic Resolution

Abstract

An iridium/f-amphol catalytic system for the enantioselective hydrogenation of α-substituted β-ketoesters via dynamic kinetic resolution is reported. The desired anti products were obtained in high yields (up to 98%) with good diastereoselectivity (up to 96:4 diastereometic ratio (dr)) and excellent enantioselectivity (up to >99% enantiomeric excess (ee)). A catalytic model is proposed to explain the stereoselectivity.

Chiral α-Amino Acid/Palladium-Catalyzed Asymmetric Allylation of α-Branched β-Ketoesters with Allylic Amines: Highly Enantioselective Construction of All-Carbon Quaternary Stereocenters

“…Melting points are uncorrected. ( E )-3-(Naphthalen-2-yl)­prop-2-en-1-amine, ( E )-3-(furan-2-yl)­prop-2-en-1-amine, amines 1a – p , 1s , 1u – y , − , ammonium salt 1i , β-ketoesters 2h and 2j , and catalysts 4a , 4b , 4d , and 4f were prepared according to literature procedures.…”

Atropselective Dibrominations of a 1,1′‐Disubstituted 2,2′‐Biindolyl with Diverging Point‐to‐Axial Asymmetric Inductions. Deriving 2,2′‐Biindolyl‐3,3′‐diphosphane Ligands for Asymmetric Catalysis

“…[47] Hydro-genating ethyl tetralonecarboxylate (25 c), ar acemic substrate,e ntailed dynamic kinetic resolutions.T hey provided 76-87 %ofthe b-hydroxyesters 26 c as a94:6 trans,cis mixture using (M)-BINAP (1)orwith perfect trans-selectivities using (R,R,M)-or (R,R,P)-14.T he ees of trans-26 c were 84 % employing 1,98% employing (R,R,M)-14,and 96 %employing (R,R,P)14.T he last-mentioned stereoselectivities are unmatched in the literature. [48] Our pair of ligands (R,R,M)-14 and (R,R,P)-14 transformed each set of reactants both from Table 1orT able All in all, we synthesized two 2,2'-biindolyl-based diphosphane ligands,( R,R,M)-and (R,R,P)-14,a tropselectively. They performed promisingly in asymmetric allylations and hydrogenations and outperformed (M)-BINAP (1)s everal times.T he atropselectivity-determining step was an aromatic dibromination.…”

Dynamic Kinetic Resolution of γ-Substituted Cyclic β-Ketoesters via Asymmetric Hydrogenation: Constructing Chiral Cyclic β-Hydroxyesters with Three Contiguous Stereocenters

“…By contrast, the catalytic asymmetric hydrogenation of configurationally labile α-substituted β-ketoesters via dynamic kinetic resolution (DKR) holds the potential of providing chiral β-hydroxy esters bearing two vicinal chiral centers with high efficiency (Scheme a) and has been successfully applied to the synthesis of chiral drugs and bioactive natural products . The success of this process relies upon the acidity of the α-C–H that facilitates the racemization of α-chiral center through an achiral enolate intermediate . However, the resolution of racemic α,γ-disubstituted β-ketoesters for the construction of chiral β-hydroxy esters with three contiguous stereocenters through catalytic asymmetric hydrogenation remains a significant challenge due to the less acidic γ-C–H of β-ketoesters (Scheme b), despite its enormous potential synthetic utility.…”